Name	Retinopathy
ICD	ICD-11: 9B71

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[1]
Response Summary	KAT1 triggers YTHDF2-mediated Integrin beta-1 (ITGB1) mRNA instability to alleviate the progression of DR.
Responsed Disease	Diabetic retinopathy [ICD-11: 9B71.0]
Target Regulator	YTH domain-containing family protein 2 (YTHDF2)		READER	Regulator Info
Target Regulation	Down regulation
Pathway Response	PI3K-Akt signaling pathway			hsa04151
Cell Process	RNA stability
In-vitro Model	RMECs (Retinal microvascular endothelial cells (RMECs) purchased from Olaf (Worcester, MA, USA))
	rMCs (Retinal Muller cells (rMCs) from Kerafast Inc. (Boston, MA))
In-vivo Model	Male mice (8-10 weeks old, SLAC Laboratory Animal Co., Ltd., Shanghai, China) were administrated with STZ through intraperitoneal injection (I.P) for continuous 5 days (d).

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[2]
Response Summary	METTL3 knockout in vivo decreased avascular area and pathological neovascular tufts in an oxygen-induced retinopathy model and inhibited alkali burn-induced corneal neovascularization.
Responsed Disease	Retinopathy [ICD-11: 9B71]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Cell Process	Cell viability
	Cell proliferation
	Cell migration
In-vitro Model	HUVEC-C	Normal	Homo sapiens	CVCL_2959
In-vivo Model	Mettl3flox/flox mice were crossed with the transgenic Cdh5-CreERT2 mice to generate the Mettl3-ecKO mice. Cdh5-Cre Mettl3flox/flox mice received an intragastric injection of 50 ul tamoxifen (1 mg/mL) at P1-P3 and P5 for Cre activation and Mettl3 knockout. After Mettl3 knockout, the mouse pups and their nursing mothers were exposed to 75% oxygen (hyperoxia) from P7 to P12 in an incubator chamber. Then, the pups were returned to normal oxygen conditions (normoxia).

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[3]
Response Summary	Lower expression TNF alpha-induced protein 3 (TNFAIP3) resulted in the enhanced M1 polarization of retinal microglia in diabetic retinopathy, which was caused by ALKBH5 mediated m6A modification.
Responsed Disease	Diabetic retinopathy [ICD-11: 9B71.0]
Target Regulator	RNA demethylase ALKBH5 (ALKBH5)		ERASER	Regulator Info
Target Regulation	Down regulation
In-vitro Model	BV-2	Normal	Mus musculus	CVCL_0182
In-vivo Model	The male Sprague-Dawley rats (8 weeks old, 200-220 g) were purchased from the Laboratory Animal Center of Sun Yat-sen University. Streptozotocin (Sigma, USA) was given by intraperitoneal injection at a dose of 60 mg/Kg to induce diabetics rats, while the control rats were given by empty citrate buffer. One week after induction, those rats with blood glucose levels > 16.7 mmol/L for three times were considered as successful inducted diabetes. All the rats did not receive insulin during the experiments.In the intraocular injection experiments, rats confirmed as the DM model (blood glucose levels > 16.7 mmol/L for three times) were anesthetized with an intraperitoneal injection of sodium pentobarbital (50 mg/Kg). A total of 10 ul DMEM with 1*109 TU lentiviruses (A20-overexpression, OE-A20 group) or the same volume of DMEM with control lentiviruses (OE-NC group) was injected into the vitreous cavity using a 33-gauge needle. This treatment was performed one time per month, and the rats were sacrificed for further experiments at the 3 months.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[4]
Response Summary	METTL3 involves in the pathogenesis of diabetic retinopathy (DR). Both METTL3 mRNA and hsa-miR-25-3p were low-expressed in the peripheral venous blood samples of diabetes mellitus (DM) patients compared to normal volunteers, and high-glucose inhibited METTL3 and miR-25-3p expressions in RPE cells. Overexpression of METTL3 attenuates high-glucose induced RPE cell pyroptosis by regulating miR-25-3p/PTEN/Akt signaling cascade through DGCR8.
Responsed Disease	Diabetic retinopathy [ICD-11: 9B71.0]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	PI3K-Akt signaling pathway			hsa04151
Cell Process	Cell viability
	Cell apoptosis
In-vitro Model	ARPE-19	Normal	Homo sapiens	CVCL_0145

Ref 1	KAT1 triggers YTHDF2-mediated ITGB1 mRNA instability to alleviate the progression of diabetic retinopathy. Pharmacol Res. 2021 Aug;170:105713. doi: 10.1016/j.phrs.2021.105713. Epub 2021 Jun 5.
Ref 2	Role of METTL3-Dependent N(6)-Methyladenosine mRNA Modification in the Promotion of Angiogenesis. Mol Ther. 2020 Oct 7;28(10):2191-2202. doi: 10.1016/j.ymthe.2020.07.022. Epub 2020 Jul 25.
Ref 3	ALKBH5-Mediated m(6)A Modification of A20 Regulates Microglia Polarization in Diabetic Retinopathy. Front Immunol. 2022 Mar 1;13:813979. doi: 10.3389/fimmu.2022.813979. eCollection 2022.
Ref 4	Overexpression of METTL3 attenuates high-glucose induced RPE cell pyroptosis by regulating miR-25-3p/PTEN/Akt signaling cascade through DGCR8. Aging (Albany NY). 2020 May 4;12(9):8137-8150. doi: 10.18632/aging.103130. Epub 2020 May 4.