Application of prostaglandin E2 in preparation of medicine for treating retina injury caused by blue light exposure

Abstract

The invention belongs to the technical field of medicines, and particularly relates to application of prostaglandin E2 in preparation of a medicine for treating retina injury caused by blue light exposure. The prostaglandin E2 medicine or the medicine composition is used for preventing or treating retina injury caused by blue light exposure, the medicine or the medicine composition has the functions of relieving shortening of a retina photoreceptor cell layer and relieving decline of retina electrophysiology a waves and b waves, and then pathological changes related to retina diseases can be improved.

Description

Technical Field

[0001] The present invention belongs to the field of medical technology, and specifically relates to the application of prostaglandin E2 in the preparation of a medicine for treating retinal damage caused by blue light exposure. Background Art

[0002] The information disclosed in this background technology section is only intended to enhance the understanding of the overall background of the invention, and should not necessarily be regarded as an admission or any form of suggestion that the information constitutes the prior art already known to a person skilled in the art.

[0003] Blue light is the light with the shortest wavelength in the visible spectrum and has relatively high energy. It can penetrate the cornea and lens to reach the retina, causing photochemical damage to the retina and leading to a variety of eye diseases such as macular degeneration, thereby inducing irreversible photochemical damage, also known as blue light damage (BLD). However, there is currently no effective drug intervention to prevent or treat retinal damage caused by blue light exposure.

[0004] The recent emergence of advanced light technologies exposes people to blue light from many different artificial light sources, such as computers, mobile phones, and light-emitting diodes. However, long-term and excessive blue light exposure is considered a risk factor for retinal degeneration. Increasing evidence shows that blue light induces photochemical defects in the retina, leading to cataracts, macular degeneration, and many other eye diseases, so preventive and therapeutic measures must be taken to alleviate blue light disease.

[0005] There are some blue light protection products, such as blue light protection glasses, goggles and blue light filtering software, which can partially prevent blue light disease. In addition, antioxidants have also shown some potential in improving photoreceptor cell degeneration in BLD animal models. However, there are currently no effective drug interventions for the prevention or treatment of BLD. Summary of the invention

[0006] In view of the problems existing in the prior art, the present invention provides the use of prostaglandin E2 in the preparation of drugs for treating retinal damage caused by blue light exposure. Prostaglandin E2 is the most abundant prostaglandin in the human body and can induce vasodilation or contraction, which is particularly important in processes such as embryo implantation, renal hemodynamic regulation, blood pressure control, childbirth and gastrointestinal motility. Therefore, it is mainly used to assist in production and the treatment of diseases such as peptic ulcers and asthma. During the research process, the inventors found that prostaglandin E2 can protect the structure and function of the retina from damage by blue light. This shows that prostaglandin E2 may be an effective drug for preventing and treating BLD-related retinal diseases.

[0007] In order to achieve the above object, the present invention adopts the following technical solution: The first aspect of the present invention provides the use of prostaglandin E2 in the preparation of a drug for treating retinal damage caused by blue light exposure.

[0008] Preferably, the drug for treating retinal damage caused by blue light exposure has at least one of the following functions (1) to (2): (1) Reduce the shortening of the retinal photoreceptor layer; (2) Alleviate the decline of retinal electrophysiological a wave and b wave.

[0009] Preferably, the prostaglandin E2 solution is administered through the vitreous cavity, with an administration dose of 0.3-0.6 μL, preferably 0.5 μL.

[0010] Preferably, the concentration of the prostaglandin E2 solution is (0.45-0.55)×10 -3 M.

[0011] Preferably, the prostaglandin E2 solution is obtained by first dissolving prostaglandin E2 powder in DMSO solution and then diluting it with 0.9% by mass saline at a volume ratio of 1:10.

[0012] The second aspect of the present invention provides a pharmaceutical composition comprising the prostaglandin E2 described in the first aspect.

[0013] Preferably, the pharmaceutical composition further comprises a biologically acceptable carrier.

[0014] Further preferably, the biologically acceptable carrier includes but is not limited to lactose, glucose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, gum arabic, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methyl hydroxybenzoate, propyl hydroxybenzoate, talc, magnesium stearate and mineral oil.

[0015] The beneficial effects achieved by one or more technical solutions of the present invention are as follows: (1) The present invention can effectively reduce the shortening of the retinal photoreceptor cell layer caused by blue light exposure by injecting prostaglandin E2 into the vitreous body, thereby improving the damage to the retinal structure.

[0016] (2) The present invention can effectively alleviate the decline of retinal electrophysiological a-wave and b-wave in BLD mice after vitreous injection of prostaglandin E2, which indicates that vitreous injection of prostaglandin E2 can effectively improve the abnormal retinal function caused by blue light irradiation.

[0017] (3) Prostaglandin E2 can successfully rescue the damage to retinal structure and function caused by blue light exposure and improve pathological changes related to retinal diseases. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] The accompanying drawings in the specification, which constitute a part of the present invention, are used to provide a further understanding of the present invention. The exemplary embodiments of the present invention and their descriptions are used to explain the present invention and do not constitute improper limitations on the present invention.

[0019] Figure 1 This is a schematic diagram of the present invention using prostaglandin E2 in the preparation of a drug for treating retinal damage caused by blue light exposure; Figure 2 This is a schematic diagram of the construction of the BLD mouse model in Example 1 of the present invention; Figure 3 This is a schematic diagram of the vitreous injection of prostaglandin E2 in BLD mice in Example 1 of the present invention; Figure 4 The morphological and structural changes of the mouse retina were analyzed by H&E staining in Experimental Example 1 of the present invention; Figure 5 This is a statistical graph of the quantitative thickness of the outer nuclear layer of the retina of mice in the vitreous injection of prostaglandin E2 group in Experimental Example 1 of the present invention; Figure 6 This is a statistical graph of the quantitative thickness of the retinal outer nuclear layer of mice in the vitreous injection DMSO group in Experimental Example 1 of the present invention; Figure 7 The ERG recordings of mice in the vitreous injection prostaglandin E2 group and the DMSO group in Experimental Example 2 of the present invention; Figure 8 This is a statistical chart of the quantitative amplitude of the retinal a-wave and b-wave of mice in the vitreous injection of prostaglandin E2 group in Experimental Example 2 of the present invention, where **** means p<0.0001, and the difference is extremely significant; Fig. 9 This is a statistical diagram of the quantitative amplitude of the retinal a-wave and b-wave of the mice in the vitreous injection DMSO group in Experimental Example 2 of the present invention, where **** means p<0.0001, and the difference is extremely significant. DETAILED DESCRIPTION

[0020] It should be noted that the following detailed descriptions are exemplary and are intended to provide further explanation of the present invention. Unless otherwise specified, all technical and scientific terms used in the present invention have the same meanings as those commonly understood by those skilled in the art to which the present invention belongs.

[0021] The present invention will be further described in detail below in conjunction with specific embodiments. It should be noted that the specific embodiments are intended to explain the present invention rather than to limit it.

[0022] Embodiment 1: (1) Construction of BLD mouse model C57BL / 6J mice were used to establish a mouse model of retinal damage caused by blue light exposure. Both male and female mice were used, and gender balance was performed in all experiments. Eight-week-old mice were used for light exposure experiments. After one day of dark adaptation, the mice were dilated with 0.5% tropicamide-phenylephrine for 30 minutes, and then the pupils were dilated before light treatment. The light sources for light treatment were blue LED (456 nm) and white LED (583 nm), and the LED light board was fixed to the cage wall (10 cm high) and 30 cm away from the mice. The ambient temperature during the light treatment was maintained at 25±1.5°C. Mice were exposed to blue light or white light (600lux or 2000lux) for 2 hours per day for 3 days. After light exposure, the mice were subjected to a normal light / dark cycle for 3 days, and finally the mice were adapted to a dark environment for 1 day, and the BLD mouse model was established (as shown in Figure 2A). Figure 2 as shown).

[0023] The specific groups are as follows: Control group: WL600: mice were exposed to 600 lux white light for 2 h per day for 3 days.

[0024] WL2000: Mice were exposed to 2000 lux white light for 2 h per day for 3 days.

[0025] Experimental groups: BL600: mice were exposed to 600 lux blue light for 2 h per day for 3 days.

[0026] BL2000: Mice were exposed to 2000 lux blue-white light for 2 h per day for 3 days.

[0027] After the model was constructed, the mice were examined for fundus. The results showed that compared with the control group, three days after blue light exposure, drusen appeared in the fundus of the mice, and as the intensity of blue light increased, these warts became more and more numerous. Drusen are colloid or transparent bodies caused by abnormal deposition of abnormal metabolites of pigment epithelial cells on the retina and are a symptom of age-related macular degeneration. This indicates that the BLD mouse model was successfully constructed.

[0028] (2) Intravitreal injection of prostaglandin E2 in BLD mice rescues retinal structural and functional damage The mice were anesthetized by inhalation of 2% isoflurane and 50 μL of 0.5% oxybuprocaine hydrochloride was dripped onto the corneal surface. The iris was dilated using 0.5% tropicamide phenylephrine, and 0.5 μL of prostaglandin E2 solution (prostaglandin E2 powder was dissolved in DMSO to a final concentration of 0.5×10 -3M, diluted 1:10 with 0.9% saline). After injection, apply 0.5% propacaine and tobramycin to the eye to minimize pain and reduce the risk of inflammation (e.g. Figure 1 and Figure 3 as shown).

[0029] According to different vitreous injection drugs, they were divided into groups again, and the specific groups are as follows: DMSO (control group): WL600, WL2000, BL600, BL2000 PGE2 (experimental group): WL600, WL2000, BL600, BL2000 Test Example 1: This test example tests the retinal structure status of each group in Example 1 In this experiment, H&E staining was performed on each group to analyze the morphological structure of the mouse retina. Figure 4 As shown, it is found that: In the DMSO group, compared with the white light group, the outer nuclear layer (ONL) of the retina of the blue light group was significantly shortened, and as the intensity of blue light increased, the shortening of the outer nuclear layer became more obvious, while the thickness of the inner nuclear layer (INL) did not change significantly. The outer nuclear layer of the retina is the cell body of the photoreceptor cells, which indicates that blue light exposure causes damage to the retinal photoreceptor cells. In the PGE2 group, after blue light exposure, the thickness of the outer nuclear layer (OS) of the retina did not change significantly ( Figure 4 ), indicating that prostaglandin E2 can protect the mouse retinal structure from blue light damage.

[0030] In this test example, the thickness of the outer nuclear layer of the mouse retina is quantitatively counted. Figures 5 and 6 As shown, because the thickness of the outer nuclear layer at different positions of the retina is different, the present invention takes the optic nerve as the center, measures the thickness of the outer nuclear layer every 200 microns to the left and right, and counts ten points for each retina to make a line graph of the thickness of the outer nuclear layer of the retina, so as to more accurately compare the changes in the thickness of the outer nuclear layer of the retina; Specific findings: In the DMSO group, compared with the white light irradiation group, the outer nuclear layer (OS) of the retina of mice in the blue light irradiation group was significantly shortened, while the thickness of the inner nuclear layer (IS) did not change significantly ( Figure 5 In the PGE2 group, after vitreous injection of PGE2, the thickness of the retinal outer nuclear layer (OS) did not change significantly after exposure to blue light, indicating that prostaglandin E2 can protect the retinal structure of mice from blue light damage ( Figure 6 ).

[0031] It can be seen from this that the present invention can effectively reduce the shortening of the retinal photoreceptor cell layer caused by blue light exposure by injecting prostaglandin E2 into the vitreous body, thereby improving the damage to the retinal structure.

[0032] Experimental Example 2: This experimental example tested the retinal function of each group in Example 1 through retinal electrophysiological experiments. In this test example, ERG recording was performed on mice in each group. Figure 7 As shown in Figure 1, retinal electrophysiology (ERG) is a retinal integrated potential response induced by flash stimulation, which can evaluate the function of the living retina. The a wave reflects the function of photoreceptor cells, and the b wave reflects the function of bipolar cells, Muller cells, etc.

[0033] Specific findings: ERG recording results showed that in the DMSO group, compared with the white light group, the amplitudes of the a and b waves in the blue light group were significantly reduced, and the amplitudes of the a and b waves decreased more significantly with the increase of the blue light intensity. In the PGE2 group, the amplitude changes of the a and b waves were significantly reduced after blue light exposure. Figure 7 ), indicating that prostaglandin E2 can protect retinal function from blue light damage.

[0034] In this experiment, the amplitudes of the a-wave and b-wave of the retina of mice in each group were quantitatively counted. Figures 8 and 9 As shown, the a-wave amplitude is measured from baseline to a-wave trough, and the b-wave amplitude is measured from a-wave trough to b-wave peak.

[0035] Specific findings: ERG recording results showed that in the DMSO group, compared with the white light group, the amplitudes of the a and b waves in the blue light group were significantly reduced, and as the intensity of blue light increased, the amplitudes of the a and b waves decreased more significantly ( Figure 8 ).

[0036] Specifically, under 600 lux light, the a-wave amplitude change value of the blue light group mice was 203 μV, and the b-wave amplitude change value was 501 μV compared with that of the white light group mice; under 2000 lux light, the a-wave amplitude change value of the blue light group mice was 265 μV, and the b-wave amplitude change value was 600 μV compared with that of the white light group mice.

[0037] In the PGE2 group, after blue light irradiation, the amplitude changes of a-wave and b-wave were significantly reduced compared with those in the DMSO group ( Fig. 9 ), indicating that prostaglandin E2 can protect retinal function from blue light damage.

[0038] Specifically, after intravitreal injection of PGE2, under 600 lux light, the a-wave amplitude change of the mice in the blue light group was 102 μV, and the b-wave amplitude change was 321 μV compared with that in the white light group; under 2000 lux light, the a-wave amplitude change of the mice in the blue light group was 182 μV, and the b-wave amplitude change was 422 μV compared with that in the white light group.

[0039] It can be seen that the present invention can effectively alleviate the decline of retinal electrophysiological a wave and b wave in BLD mice after vitreous injection of prostaglandin E2, which shows that vitreous injection of prostaglandin E2 can effectively improve the abnormal retinal function caused by blue light irradiation.

[0040] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. For those skilled in the art, the present invention may have various modifications and variations. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included in the protection scope of the present invention.

Claims

1. Application of prostaglandin E2 in the preparation of drugs for treating retinal damage caused by blue light exposure.

2. The use according to claim 1, characterized in that The function of the drug for treating retinal damage caused by blue light exposure has at least one of the following functions (1) to (2): (1) Reduce the shortening of the retinal photoreceptor layer; (2) Alleviate the decline of retinal electrophysiological a wave and b wave.

3. The use according to claim 1, characterized in that The prostaglandin E2 solution is administered through the vitreous cavity, with an administration dose of 0.3-0.6 μL.

4. The use according to claim 3, characterized in that The administration dose of the prostaglandin E2 solution was 0.5 μL.

5. The use according to claim 1, characterized in that The concentration of the prostaglandin E2 solution is (0.45-0.55)×10 -3 M.

6. The use according to claim 5, characterized in that The prostaglandin E2 solution is obtained by first dissolving prostaglandin E2 powder in a DMSO solution, and then diluting the solution with 0.9% by mass saline at a volume ratio of 1:

10.

7. A pharmaceutical composition, characterized in that The invention relates to a prostaglandin E2 comprising the prostaglandin E2 according to any one of claims 1 to 6.

8. The pharmaceutical composition according to claim 7, characterized in that The product also includes a biologically acceptable carrier.

9. The pharmaceutical composition according to claim 8, characterized in that The biologically acceptable carrier includes, but is not limited to, lactose, glucose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, gum arabic, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methyl hydroxybenzoate, propyl hydroxybenzoate, talc, magnesium stearate and mineral oil.

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