Applications of small molecule drug (+)-JQ1 in drugs for treating geographic atrophy type age-related macular degeneration
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A macular degeneration, -JQ1 technology, applied in the field of macular degeneration
Inactive Publication Date: 2021-03-26
ZHONGSHAN OPHTHALMIC CENT SUN YAT SEN UNIV
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However, there is no relevant report that (+)-JQ1 can inhibit the cGAS-STING signaling pathway
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Embodiment 1
[0029] Example 1 The cGAS-STING signaling pathway is activated in the retina of the sodium iodate-induced age-related macular degeneration mouse disease model
[0030] 1. Experimental method
[0031] (1) Model construction
[0032] Mice were injected intraperitoneally with sodium iodate (0.5%, prepared in PBS) at a dose of 35 mg / kg to establish a mouse model of age-related macular degeneration.
[0033] (2) Mouse fundus photography and fundus fluorescein angiography
[0034] Mouse fundus photography and fluorescein fundus angiography were performed before sodium iodate injection and three days after sodium iodate injection. The specific operations were as follows:
[0035] Before photographing the fundus of the mice, the mice were anesthetized with 4% chloral hydrate (100 μl / 10 g), 1-2 drops of compound tropicamide eye drops were used to dilate the pupils, and hypromellose gel was used to lubricate the cornea. Thereafter, fundus photographs were taken using the Micron IV re...
Embodiment 2
[0053] Example 2 (+)-JQ1 can inhibit the activation of the cGAS-STING signaling pathway and the downstream inflammatory response in the retina of the geographic atrophy age-related macular degeneration mouse model induced by sodium iodate, and has protection against retinal damage effect
[0054] 1. Experimental method
[0055] Mice were injected intraperitoneally with sodium iodate (0.5%, prepared in PBS) at a dose of 35 mg / kg to establish a mouse model of age-related macular degeneration.
[0056] Two hours after the sodium iodate injection, (+)-JQ1 (+)-JQ1 (5 mg / ml) was injected intraperitoneally into the (+)-JQ1 treatment group at a dose of 50 mg / kg, and the same volume of sodium iodate treatment group was injected intraperitoneally. Drug solvent (2% DMSO, 30% Polyoxyethylene300, 5% Tween80), (+)-JQ1 and drug solvent were injected for 3 days, once a day. Mice in the control group were injected with an equal volume of sterile phosphate-buffered saline (PBS).
[0057] Fol...
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Abstract
The invention discloses applications of a small molecule drug (+)-JQ1 in drugs for treating geographic atrophy type age-related macular degeneration, and specifically discloses the small molecule drug(+)-JQ1 having effects of inhibiting cGAS-STING signal pathways and regulatory and anti-inflammatory effects of the small molecule drug on autoimmunity. In a mouse disease model of sodium iodate injection induced geographic atrophy type age-related macular degeneration, the (+)-JQ1 is firstly provided that the (+)-JQ1 can inhibit the expression of cGAS and STING genes and achieve immunoregulationand anti-inflammatory effects by inhibiting the functions of the cGAS-STING signal pathways. The inhibition of the (+)-JQ1 on the cGAS-STING signal pathways and the anti-inflammatory effects of the(+)-JQ1 in the disease model of geographic atrophy type age-related macular degeneration are a promising clinical strategy of new use for old drugs, so that reference can be provided for researches on small molecular compounds for anti-autoimmune response and treatment of age-related macular degeneration diseases.
Description
technical field [0001] The invention relates to the technical field of macular degeneration, in particular to the application of a small molecule drug (+)-JQ1 in the treatment of geographic atrophy type age-related macular degeneration. Background technique [0002] Macular degeneration is a relatively common eye disease, which is divided into age-related macular degeneration and juvenile macular degeneration. Geographic atrophy is one of the types of age-related macular degeneration, which affects about five million patients worldwide and currently has no effective treatment. Geographic atrophic age-related macular degeneration results from progressive retinal pigment epithelial degeneration and atrophy, and the death of photoreceptor cells due to retinal pigment epithelial degeneration results in permanent visual impairment. [0003] Studies have shown that although age-related macular degeneration is a multifactorial disease, the disorder of autoimmune function plays an ...
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