Clinical Role of Epigenetics and Network Analysis in Eye Diseases: A Translational Science Review

Table 1

Pathogenic epigenetic modifications in different ocular diseases.

Disease	Epigenetic modification	Gene	Effect	Phenotypic outcome	References
Pterygium	DNA hypermethylation	TGM2	Reduced protein expression
	DNA hypomethylation	MMP2	Increased protein expression	Fibrosis and neovascular changes	[12]
	DNA hypomethylation	CD24	Increased protein expression
	Upregulation of hsa-miR-143a-3p, hsa-miR-181a-2-3p, hsa-miR-377-5p, and hsa-miR-411a	—	Reduced mRNA and protein expression	—	[13]
GCD2	H3K4 hypermethylation; H3K27 hypomethylation	TGFBIp	Increased gene expression	Increased expression of ECM genes	[14]
Cataract	DNA hypermethylation	GSTP1	Reduced mRNA and protein expression	Increased oxidative stress	[15]
	DNA hypermethylation	OGG1	Reduced mRNA and protein expression	Increased oxidative stress	[16]
	DNA hypermethylation; H3K9 hypermethylation	ERCC6	Reduced mRNA and protein expression	Increased rate of apoptosis	[17]
Glaucoma	DNA hypomethylation	TGF-β1	Increased protein expression	Increased ECM protein production and accumulation	[18]
PEX	DNA hypermethylation	LOXL1	Reduced protein expression	Failure of elastic fiber homeostasis	[19]
Diabetic retinopathy	Downregulation of hsa-miR-29b-1 and hsa-miR-200b	//	Overexpression of gene target	Deregulation of cellular survival/apoptosis, ECM cytoskeleton signaling	[20]
	5hmC	RAC1	Increased binding of NF-kB	Increased ROS levels	[21]
AMD	DNA hypermethylation	GSTM1/5	Reduced protein expression	Increased susceptibility to oxidative stress	[22]
RB	Upregulation of hsa-miR-494, hsa-let-7e, hsa-miR-513a-1, hsa-miR-513a-2, hsa-miR-518c, hsa-miR-129-1, hsa-miR-129-1, hsa-miR-129-2, hsa-miR-198, hsa-miR-492, hsa-miR-498, hsa-miR-320, hsa-miR-503, and hsa-miR-373	—	Deregulation of gene targets	Associated to insurgence/progression of retinoblastoma tumorigenesis through hypoxia, immune escape, reduction of apoptosis	[23]

TGM2: transglutaminase 2; MMP2: matrix metalloproteinase 2; CD24: CD24 molecule; TGFBIp: transforming grow factor B-induced; GSTP1: pi-class glutathione-S-transferase; OGG1: 8-oxoguanine DNA glycosylase 1; ERCC6: excision repair 6 chromatin remodeling factor; LOXL1: lysyl oxidase-like 1; RAC1: rac family small GTPase 1; GSTM1/5: glutathione S-transferase isoform mu1/mu5; AMD: age-related macular degeneration; ECM: extracellular matrix; GCD2: granular corneal dystrophy type 2; 5hmC: 5-hydroxymethyl cytosine; NF-kB: nuclear factor kappa-light-chain-enhancer of activated B cells; PEX: pseudoexfoliation syndrome; RB: retinoblastoma; ROS: reactive oxygen species.