Use of a substance which specifically binds to an NSE protein or to a gene coding therefor for the manufacture of a diagnostic or prognostic product for ARN

Abstract

The present application relates to the field of medicine, in particular to the use of a substance specifically binding to NSE protein or its encoding gene in the preparation of a diagnostic product or a prognostic product for ARN. By detecting NSE protein or its encoding gene, the optic neuropathy caused by acute retinal necrosis can be understood, and doctors can identify ARN conditions earlier, so as to promptly implement appropriate medical intervention. Therefore, the present application can not only significantly reduce the risk of retinal detachment and vision loss, but also assist clinicians in accurately assessing the severity of the disease and predicting the possibility of vision recovery, which can promote the individualization and precision of treatment. In addition, by avoiding unnecessary drug use and wasting of medical resources, it also brings economic benefits, which benefits patients and society.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of medicine, in particular to the use of a substance specifically binding to NSE protein or its encoding gene in the preparation of a diagnostic product or a prognostic product for ARN. BACKGROUND

[0002] Acute Retinal Necrosis (ARN) is a rare but potentially devastating intraocular inflammatory disease that can affect people of any age. ARN is mainly caused by viral infection, and the pathogens include Varicella-zoster Virus (VZV), Herpes Simplex Virus (HSV) and Cytomegalovirus (CMV). The pathological mechanism of ARN involves direct invasion of viral to retinal nerve cells, triggering local inflammatory response. Viruses spread to the retina through the trigeminal ganglion or through the blood, triggering retinitis. Inflammatory response leads to retinal vasculitis, and further causes retinal ischemia and tissue necrosis. The clinical manifestations of ARN include vitritis, occlusive retinal arteriolar vasculitis and confluential necrotizing retinitis. Patients may have symptoms such as decreased vision, eye pain, photosensitivity, and floaters. Fundus examination can see white or yellowish necrotic lesions on the retina, which are usually located in the mid-peripheral part of the retina and can rapidly expand. Early diagnosis of ARN faces great challenges. Due to the lack of specificity of early symptoms, and the similarity with other retinal diseases, especially uveitis, it is difficult to diagnose. Early literature reports show that the misdiagnosis rate of ARN can be as high as more than 70%. The treatment of ARN usually includes antiviral drugs, corticosteroids, and in some cases, laser therapy or surgery. However, the timeliness and effectiveness of treatment are crucial to improve the prognosis. Currently, the problems in treatment include insufficient timeliness, lack of targeted antiviral treatment, and insufficient control of disease progression. If ARN cannot be diagnosed and treated in time, patients may have a high incidence of retinal detachment, leading to severe vision loss or even blindness. Therefore, early and correct diagnosis and timely treatment, striving to control the development of the disease before retinal detachment occurs, are of great significance to improve the prognosis of ARN patients.

[0003] In summary, the current diagnosis of acute retinal is mainly determined by clinical ophthalmologists through the clinical manifestations of patients, however, due to the difficulty of observation caused by vitreous opacity and the subjectivity of physical examination, the early correct diagnosis rate of this disease is low, and misdiagnosis and missed diagnosis are easy to occur. Clinically, there is a need for objective and accurate biomarkers to help early correct diagnosis of ARN. Given the severity of ARN and the urgency of treatment, it is necessary to develop new diagnostic tools.

[0004] Enolases are ubiquitous in living organisms and are key enzymes in the glycolysis pathway. They have three subunits with different immune properties: α, β, and γ. The γγ dimer form is found only in neurons and neuroendocrine cells and is called neuron-specific enolase (NSE). Normal body fluids contain very small amounts of NSE. Neurological damage caused by viral infections, ischemia, or hypoxia can lead to NSE leakage from damaged neurons. NSE levels can preliminarily reflect the severity of neurological damage; higher NSE levels indicate more severe neurological damage and a worse prognosis. NSE detection is rapid, providing results within half an hour, making it clinically valuable. However, no information has been published regarding the correlation between NSE in the aqueous humor and aronin (ARN). Summary of the Invention

[0005] In view of the shortcomings of the prior art described above, the purpose of this invention is to provide the use of substances that specifically bind to NSE proteins or their encoding genes in the preparation of ARN diagnostic or prognostic products, thereby solving the problems in the prior art.

[0006] To achieve the above and other related objectives, the present invention provides the use of substances that specifically bind to NSE protein or its encoding gene in the preparation of diagnostic or prognostic products for retinal necrosis.

[0007] Preferably, the retinal necrosis is acute retinal necrosis (ARN).

[0008] The acute retinal necrosis diagnostic product is designed to differentiate patients with acute retinal necrosis from healthy individuals or patients with other diseases, such as uveitis.

[0009] The acute retinal necrosis diagnostic product can also be a product used to determine the severity of acute retinal necrosis.

[0010] As described above, the use of substances specifically binding to NSE proteins or their encoding genes in the preparation of ARN diagnostic or prognostic products has the following beneficial effects: it allows for objective and accurate observation of optic nerve damage caused by acute retinal necrosis; by detecting the level of NSE proteins in the aqueous humor and judging based on clinical diagnostic values, it can help clinicians diagnose ARN early, promptly adopt appropriate treatment methods, effectively reduce the risk of retinal detachment and blindness, help clinicians accurately assess disease severity and visual prognosis, achieve precision treatment, reduce drug abuse, and has significant economic benefits for patients and society. The application potential of using aqueous humor NSE protein levels as a biomarker for assessing optic nerve damage is not limited to this; it may also cover several other ophthalmic diseases that can also cause optic nerve damage, such as glaucoma, optic neuritis, and infectious endophthalmitis. This discovery provides a new direction for the early diagnosis and treatment of these diseases. Attached Figure Description

[0011] Figure 1 The graph shows the difference in NSE protein levels in the aqueous humor of ARN and UV patients according to the present invention.

[0012] Figure 2 The ROC curves are plotted based on the expression levels of NSE protein in aqueous humor samples from ARN patients and control patients.

[0013] Figure 3 The results show the correlation between the level of NSE in the aqueous humor and the percentage of clinically observed retinal necrosis area.

[0014] Figure 4 The left figure shows the trend of NSE levels in the aqueous humor during treatment, while the right figure shows the trend of the percentage of necrosis area.

[0015] Figure 5 The results of a correlation analysis between NSE levels and retinal detachment survival are shown. Detailed Implementation

[0016] Neuron-specific enolase (NSE) detection is currently mainly reported for its application in the detection of related diseases in blood and cerebrospinal fluid. Reports on NSE detection in aqueous humor are extremely rare, and studies using the detection of secreted protein expression in aqueous humor for the diagnosis of adenovirus renal lesions (ARN) are scarce. Currently, there are no reports establishing a link between NSE and ARN diagnosis. This invention collects aqueous humor from ARN patients in the disease group and uveitis patients in the control group, whose early symptoms are similar to ARN but are easily misdiagnosed and require special differential diagnosis. The expression level of NSE in the test samples is measured. If the NSE expression level is higher than the diagnostic value of 7.18 ng / mL, ARN can be diagnosed. The diagnostic value obtained through comparative analysis of the disease group and the control group has very high clinical application value. Furthermore, correlation analysis of NSE levels in aqueous humor and the percentage of retinal necrosis area yielded the correlation coefficient and linear formula, which can more objectively help clinicians understand the severity of the disease.

[0017] Based on the above, the present invention provides the use of substances that specifically bind to NSE protein or its encoding gene in the preparation of diagnostic or prognostic products for retinal necrosis.

[0018] In some embodiments of the present invention, the retinal necrosis is acute retinal necrosis (ARN).

[0019] NSE protein is a dimerizing enzyme encoded by the NSE gene. It consists of two identical subunits and has an α-β-α sandwich structure, which contributes to the enzyme's stability and catalytic activity. During glycolysis, NSE protein catalyzes the conversion of 2-phosphoglycerate (2-PG) to phosphoenolpyruvate (PEP).

[0020] In some embodiments of the present invention, the NSE protein is a wild-type NSE protein or a mutant NSE protein.

[0021] The NSE protein is a full-length sequence or a protein fragment, meaning that the acute retinal necrosis diagnostic or prognostic product includes a substance that can specifically bind to the full-length sequence or protein fragment of the NSE protein.

[0022] The NSE protein or its encoding gene is derived from an animal, preferably a mammal; the mammal is preferably a rodent, even-toed ungulate, perissodactyl, lagomorph, primate, etc. The mammal includes, for example, humans, non-human primates (e.g., monkeys), mice, pigs, cattle, goats, rabbits, rats, guinea pigs, hamsters, monkeys, or other non-human mammals; non-mammals include, for example, non-mammal vertebrates, such as birds or fish, and non-mammal invertebrates.

[0023] In a preferred embodiment, the NSE protein or its encoding gene is derived from humans. The human NSE gene is located in the 1p36.2 region of human chromosome, and the NSE protein encoded by this gene consists of 495 amino acid residues.

[0024] The substance that specifically binds to the NSE protein or its encoding gene is not specifically limited, as long as it can specifically bind to the NSE protein or its encoding gene. For example, it can be an antibody, a functional fragment of an antibody, a conjugated antibody, a nucleic acid molecule, a lipid, a small chemical molecule, a polypeptide, a protein, a lentivirus, an adeno-associated virus, a nanoparticle, a liposome, an extracellular vesicle, or a cell.

[0025] The acute retinal necrosis diagnostic product is designed to differentiate patients with acute retinal necrosis from healthy individuals or patients with other diseases, such as uveitis.

[0026] The acute retinal necrosis diagnostic product can also be used to determine the severity of acute retinal necrosis. Higher expression levels of NSE protein or its encoding gene detected by the acute retinal necrosis diagnostic product indicate more severe acute retinal necrosis. Clinically, the severity of acute retinal necrosis can be measured as the percentage of retinal necrosis area.

[0027] The acute retinal necrosis prognostic product refers to a product used to predict disease progression, such as a product that predicts the probability of retinal detachment (RD) leading to vision loss.

[0028] The effective ingredient in the diagnostic or prognostic product may be solely a substance that specifically binds to the NSE protein or its encoding gene, or it may contain other substances. That is, the substance used to detect the NSE protein or its encoding gene is the sole or one of the effective ingredients of the product. The product can be used in combination with other products or alone.

[0029] The product can be a single-component substance or a multi-component substance.

[0030] The product may be a commercially available reagent or kit, or a self-made reagent. A commercially available kit, for example, is an electrochemiluminescence (ECL) kit. The components of such an ECL kit may include, for example, one or more of antibodies capable of specifically binding to NSE, functional fragments of antibodies, and conjugated antibodies, as well as system buffer, measurement cell cleaning solution, pre-cleaning solution, needle washing solution, reaction cups, and sample tips.

[0031] There are no special restrictions on the form of the product; it can be in various forms such as solid, liquid, gel, semi-liquid, or aerosol.

[0032] The product is primarily designed for samples containing aqueous humor.

[0033] This invention does not specifically limit the etiology, clinical manifestations, severity, or presence of complications of acute retinal necrosis. Any acute retinal necrosis can be diagnosed using the diagnostic product of this invention.

[0034] the term

[0035] In this invention, a "marker" refers to a biomolecule or biomolecular fragment whose changes and / or detection can be associated with a specific physical condition or state. The terms "marker," "molecular marker," or "biomarker" are used interchangeably throughout this disclosure.

[0036] In this invention, the terms "patient," "subject," or "individual" can refer to an organism, and in some respects, a subject can be a human being. Subjects providing samples may include individuals at potential disease risk or individuals diagnosed with a disease. In this invention, the disease refers to ARN or uveitis.

[0037] In this invention, the terms "sample" and "sample" are used interchangeably, and the latter includes substances obtained from an individual or isolated tissue, cell or body fluid that are suitable for biomarker detection.

[0038] In this invention, "prognosis" refers to the prediction of the potential consequences of trauma or disease (e.g., ARN). Prognostic indicators include short-term and long-term efficacy indicators, including but not limited to HR, ORR, DCR, OS, PFS, DFS, and RFS. HR refers to the hazard ratio, used to compare the risk of a specific event (e.g., disease recurrence, death) occurring in two groups (e.g., the observation group and the control group) within a specific timeframe. HR calculations are typically based on survival analysis models, such as the Cox proportional hazards model. In practice, statistical software (e.g., R, SAS, SPSS) is usually used to construct the Cox model and calculate the HR. If HR > 1, the risk in the observation group is higher than that in the control group. If HR < 1, the risk in the observation group is lower than that in the control group. If HR = 1, the risks in both groups are the same. "OS" stands for "Overall Survival," which refers to the total survival time of all patients in a study; "PFS" stands for "Progression-Free Survival," which usually refers to the time during which a patient's disease has not progressed or developed resistance after treatment; "DFS" stands for "Disease-Free Survival," which usually refers to the time from randomization to disease recurrence or death (from any cause); "RFS" stands for "Recurrence-Free Survival," which usually refers to the time from the date of initial treatment to the date of recurrence or the date of the last follow-up. Clinically, median OS, median PFS, median RFS, and median DFS are generally used to express these values, representing the survival time / progression-free survival / recurrence-free survival / disease-free survival time achieved by 50% of patients.

[0039] In this invention, the "ROC curve" refers to the Receiver Operating Characteristic curve. In certain specific embodiments of this invention, the ROC curve refers to the ROC curve between the true positive rate and the false positive rate.

[0040] In this invention, the term "expression level" can refer to the concentration or amount of the gene / protein of the biomarker of this invention in the sample.

[0041] In this invention, the terms "high expression" and "high expression level" are interchangeable and, in their application, should mean at least a 5%, 10%, or 20% increase compared to a "control" or "threshold," preferably at least 30% or 50%, more preferably at least 80% or 100%, or even more significantly. For example, genes with at least one expression intensity exceeding the threshold can be repeatedly tested using Student's T-test to determine significance.

[0042] In this invention, the terms "low expression" and "low expression level" are interchangeable and, in their application, should mean a reduction of at least 5%, 10%, or 20% compared to a "control" or "threshold," preferably at least 30% or 50%, more preferably at least 80% or 100%, or even more significantly. For example, genes with at least one expression level below the threshold can be repeatedly tested using Student's T-test to determine significance.

[0043] In this invention, the setting of the "control" or "threshold" for gene or protein expression is easily determined by those skilled in the art based on the spirit of this invention. Selecting a suitable "control" or "threshold" is a routine part of experimental design. For example, statistically significant analysis of the expression levels of the corresponding genes / proteins can be performed first on samples from subjects (patients) whose prognosis / treatment efficacy is clear, and the obtained expression values ​​can be used as the "control" or "threshold".

[0044] In this invention, the term "kit" can refer to a system of materials or reagents used to implement the methods disclosed in this invention.

[0045] The sequence information of the NSE gene can be found in NCBI Gene:2026, and this invention may also cover its sequence variants in organisms.

[0046] The biomarkers disclosed in this invention can be used as diagnostic markers for assessing the development of ARN and the efficacy of treatments. This allows for understanding the disease state of an individual, evaluating or predicting prognostic disease risk, and developing treatment / medication plans.

[0047] As one approach, the method of using the aforementioned biomarkers to diagnose ARN or evaluate the prognosis of ARN includes: (1) detecting the expression level of NSE protein or gene in a subject sample; (2) based on the expression level obtained in (1): when the expression is high, it indicates that the patient has ARN, and the higher the expression level, the more severe the disease, or the poor prognosis and short survival; conversely, the absence of ARN or the good prognosis.

[0048] In this invention, when the risk value is higher than a preset threshold, it indicates the presence of ARN or a high risk of disease prognosis; when the risk value is lower than the preset threshold, it indicates the absence of ARN or a low risk of disease prognosis.

[0049] The expression level of the biomarker described in this invention can be determined according to established standard procedures well known in the art. The determination can be performed at the DNA, RNA, or protein level, for example, by detecting cDNA levels after reverse transcription of RNA using real-time quantitative PCR; or by detecting protein levels using electrochemiluminescence or ELISA.

[0050] As an alternative approach, detection can be achieved using antibodies that specifically bind to the protein of the marker.

[0051] As an alternative approach, primers that specifically amplify the markers can be designed based on their sequences for detection. Polymerase chain reaction (PCR) is a technique well-known to those skilled in the art, and its basic principle is the in vitro enzymatic synthesis of specific DNA fragments. The method of this invention can be performed using conventional PCR techniques.

[0052] The method of amplifying specific gene fragments using PCR is a well-known technique in the art, and there are no particular limitations in this invention. Labeling the amplification products can be achieved by using primers with a labeled group at the 5' end, by incorporating a labeled mononucleotide during amplification, or by adding a detection probe that specifically binds to the amplification product during hybridization. The labeled groups include, but are not limited to: digoxigenin (DIG), biotin (Bio), fluorescein and its derivatives (FITC, etc.), other fluorescent molecules (such as Cy3, Cy5, etc.), alkaline phosphatase (AP), horseradish peroxidase (HRP), etc.

[0053] The following specific examples illustrate the implementation of the present invention. Those skilled in the art can easily understand other advantages and effects of the present invention from the content disclosed in this specification. The present invention can also be implemented or applied through other different specific embodiments, and various details in this specification can also be modified or changed based on different viewpoints and applications without departing from the spirit of the present invention.

[0054] Before further describing specific embodiments of the present invention, it should be understood that the scope of protection of the present invention is not limited to the specific embodiments described below; it should also be understood that the terminology used in the embodiments of the present invention is for describing specific embodiments and not for limiting the scope of protection of the present invention; in the specification and claims of the present invention, unless otherwise expressly stated in the text, the singular forms "a", "an" and "this" include the plural forms.

[0055] When numerical ranges are given in the embodiments, it should be understood that, unless otherwise stated in the present invention, both endpoints of each numerical range and any value between the two endpoints may be selected. Unless otherwise defined, all technical and scientific terms used in this invention have the same meaning as commonly understood by one of ordinary skill in the art. In addition to the specific methods, apparatus, and materials used in the embodiments, based on the knowledge of the prior art possessed by one of ordinary skill in the art and the description of this invention, any prior art methods, apparatus, and materials similar to or equivalent to those described, apparatus, and materials in the embodiments of this invention may be used to implement the present invention.

[0056] This invention collected aqueous humor samples from 40 patients with ARN and 43 patients with uveitis (UV), and used electrochemiluminescence immunoassay to detect the expression level of NSE in the aqueous humor samples using a Roche cobas e602 instrument. Statistical analysis was then performed on the differences in NSE expression in the aqueous humor of ARN and uveitis patients. Furthermore, this invention used GraphPad Prism 9.5.1 to plot scatter plots of NSE detection concentrations and Kaplan-Meier survival curves for the two differential diagnoses, and MedCalc 19.6.4 to plot single ROC curves to analyze the specificity and sensitivity of NSE protein for ARN diagnosis. Details are as follows:

[0057] Example 1

[0058] I. Experimental Materials

[0059] The neuron-specific enolase (NSE) electrochemiluminescence kit used in this example was purchased from Roche Diagnostics GmbH, and the reagent components are shown below:

[0060] 1. Streptavidin-coated microparticles, 1 vial, 6.5ml. Magnetic microbeads containing streptavidin-coated particles, particle concentration 0.72mg / ml, containing preservatives.

[0061] 2. Biotinylated anti-NSE antibody, 1 vial, 10ml, containing biotinylated anti-NSE monoclonal antibody 18E5 (mouse-derived) 1.0mg / l, phosphate buffer 50mmol / l, pH 7.2; contains preservatives.

[0062] 3. Ru(bpy)32+ labeled anti-NSE antibody, 1 vial, 10ml. Anti-NSE monoclonal antibody 84B10 (mouse-derived) labeled with ruthenium complex, concentration 1.0mg / L (2mg / L), phosphate buffer 50mmol / L, pH 7.2, containing preservatives.

[0063] Other required materials:

[0064] 1. System Buffer (ProCell)

[0065] 2. Measuring Cell Cleaning Solution (CleanCell)

[0066] 3. Preclean solution

[0067] 4. Probewash

[0068] 5. Reaction Cup (CUP)

[0069] 6 Sample Dispensing Heads (TIP)

[0070] II. Experimental Procedure

[0071] 1. Sample collection

[0072] Aqueous humor was collected from 40 patients with aeroid retinopathy (ARN) and 43 patients with uveitis (control group). The ARN patients' ARN ...

[0073] 2. Electrochemiluminescence immunoassay for NSE content in aqueous humor

[0074] In the first stage of the reaction, the sample is incubated with biotinylated NSE monoclonal antibodies and ruthenium complex-labeled specific NSE monoclonal antibodies to form a sandwich complex. In the second step, streptavidin-coated microparticles are added, allowing the aforementioned complex to bind to the microparticles via a reaction between biotin and streptavidin. The reaction mixture is drawn into the measuring cell, and the microparticles are magnetically adsorbed onto the electrodes. Unbound material is washed away by Procell, and chemiluminescence is generated when pressure is applied to the electrodes, which is then measured by a photomultiplier tube. The instrument automatically calculates the detection result using the calibration curve of the detector.

[0075] 3. t-test analysis

[0076] Plotting a standard curve: In an Excel worksheet, plot the standard concentration on the x-axis and the corresponding OD value on the y-axis to create a linear regression curve for the standards. Calculate the NSE concentration for each sample according to the curve equation. Analyze whether there is a significant difference in NSE protein levels between the ARN group and the control group (UV group) using a t-test. The test results are as follows: Figure 1 As shown in the figure. The results indicate that, compared with UV patients, ARN patients had significantly higher levels of NSE protein in their aqueous humor, suggesting that NSE expression levels are closely related to ARN and can serve as a biomarker for ARN diagnosis.

[0077] Example 2: Accuracy, sensitivity, and specificity of ROC curve analysis

[0078] ROC curves were plotted using GraphPad Prism 9.5.1 to analyze the diagnostic value of NSE protein in ARN. Based on the expression levels of NSE protein in aqueous humor samples from 40 ARN patients and 43 control patients, ROC curves were plotted to evaluate the diagnostic ability of NSE in differentiating between ARN and UV patients.

[0079] Based on the ROC curve for differentiating ARN and UV patients using NSE protein, the NSE concentration with the highest Youden index was used as the cutoff value (i.e., the diagnostic value). Simultaneously, the corresponding AUC, 95% confidence interval, sensitivity, and specificity were calculated. The formulas for calculating sensitivity and specificity are as follows:

[0080] TPR = TP / (TP + FN)

[0081] Where TPR stands for sensitivity.

[0082] TP stands for True Positives, which is the number of samples that are correctly predicted as positive.

[0083] FN stands for False Negatives, which is the number of positive samples that are incorrectly predicted as negative.

[0084] FPR = FP / (FP + TN)

[0085] Where FPR stands for specificity.

[0086] FP stands for False Positives, which is the number of negative samples that are incorrectly predicted as positive.

[0087] TN stands for True Negatives, which is the number of samples that are correctly predicted as negative.

[0088] Test results as follows Figure 2 As shown in the figure, when NSE was used for the diagnosis of ARN, the diagnostic threshold was 7.18 ng / mL. That is, if the expression level of NSE was higher than the diagnostic threshold of 7.18 ng / mL, ARN could be diagnosed. The AUC value of the ROC curve was 0.975, the sensitivity was 92.5%, the specificity was 95.45%, and the Youden index was 0.880. The results indicate that the expression level of NSE in human aqueous humor has very high specificity, accuracy, and sensitivity in the diagnosis of ARN.

[0089] Example 3: Correlation analysis between biomarkers and the percentage of retinal necrosis area

[0090] Patients diagnosed with ARN underwent ultra-wide-angle fundus imaging (UWF) using an Optos 200Tx laser scanning ophthalmoscopy retinal imaging system. The acquired images were assessed and agreed upon by two experienced physicians regarding the percentage of active retinal necrosis. Linear regression analysis of aqueous humor NSE concentration versus the percentage of active retinal necrosis was plotted using GraphPad Prism 9.5.1, along with the dynamic changes of both outcomes after treatment. Results are shown below. Figure 3 , 4 As shown. Figure 3 As shown, the level of NSE in the aqueous humor is correlated with the clinically observed percentage of retinal necrosis area, with a correlation coefficient r of 0.6603, indicating that the expression level of NSE can reflect the severity of the disease. Figure 4 As shown, the NSE level in the aqueous humor showed a significant decreasing trend in concentration across three tests during the treatment process, consistent with the decreasing trend in the percentage of necrotic area.

[0091] Example 4: Prognostic correlation between NSE and ARN

[0092] To analyze the relationship between aqueous humor NSE concentration and retinal detachment (retinal detachment) survival rate, all ARN patients were ranked by aqueous humor NSE concentration. Using the median of 400 pg / mL as the cutoff value, patients were divided into two groups: >400 pg / mL and <400 pg / mL. Patients were followed up for a maximum of one year, and follow-up was terminated upon the occurrence of retinal detachment. Kaplan-Meier curves were plotted using GraphPad Prism 9.5.1. The results showed a significant correlation between aqueous humor NSE level and retinal detachment risk. Figure 5 (P = 0.002). Patients with NSE concentrations >400 pg / mL had a significantly increased risk of developing retinal detachment, with a hazard ratio (HR) of 5.389 (95% confidence interval, 1.853–15.6). This suggests that aqueous humor NSE can serve as a prognostic biomarker for patients with ARN.

[0093] The above embodiments are for illustrating the implementation schemes disclosed in this invention and should not be construed as limiting the invention. Furthermore, various modifications and variations of the methods listed herein will be apparent to those skilled in the art without departing from the scope and spirit of the invention. Although the invention has been specifically described in conjunction with various specific preferred embodiments, it should be understood that the invention should not be limited to these specific embodiments. In fact, various modifications as described above that are obvious to those skilled in the art to obtain the invention should be included within the scope of this invention.

Claims

1. The use of a substance that specifically binds to NSE protein in the preparation of prognostic products for acute retinal necrosis, characterized in that, The sample type of the prognostic product for acute retinal necrosis is aqueous humor.

2. The use according to claim 1, characterized in that, The NSE protein is a full-length sequence; and / or, the NSE protein is a wild-type NSE protein.

3. The use according to claim 1, characterized in that, The NSE protein is derived from animals.

4. The use according to claim 3, characterized in that, The NSE protein is derived from mammals.

5. The use according to claim 3, characterized in that, The NSE protein is derived from humans.

6. The use according to claim 1, characterized in that, The substance that specifically binds to the NSE protein is selected from antibodies and functional fragments of antibodies.

7. The use according to claim 1, characterized in that, The product for the prognosis of acute retinal necrosis is an electrochemiluminescence reagent kit.

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