Table 2 Pro-angiogenic lncRNAs

ANRIL

Upregulated in HG-treated hRECs, retinas of DR rats and the serum and vitreous of DR patients

Contribute to pathological DR vascular phenotypes and inflammation

Promote NF-kB pathway and enhances VEGF expression through interacting with p300 and EZH2, which regulates miR200b

[53, 56, 58, 63]

H19

Up- or down-regulated in Diabetics or DR,

upregulated in corneal neovascularization

proangiogenic but could inhibit endMT and inflammation

Inhibits endMT by inhibiting TGF-β1 and MAPK-ERK1/2 pathway; inhibit inflammation by sponging miR-19b that targets SIRT1; enhances angiogenesis by sponging miR-29c that targets VEGF-A

[71, 73, 76,77,78]

HDAC4-AS1

Increased in hypoxic ARPE-19 cells

unknown

Enhances HDAC4 transcription activity by recruiting HIF-1α to the HDAC4 promoter

[128]

HIF1A-AS2

Upregulate by hypoxia in ECs, and in the serum of diabetic and proliferative DR patients

Enhance EC angiogenic activities

Acts as ceRNA for miR-153-3p that targets HIF-1α

[127]

HOTAIR

upregulated in HG-treated hRECs, in

the retina of DR mice and the vitreous humor and serum from proliferative DR patients

Contribute to diabetic vascular phenotypes

Binds to PRC2 and LSD, which regulates VEGF-A, ANGPTL4, PFGF and HIF1α transcription.

[64,65,66,67]

HOTTIP

Increased in STZ-induced DR mice and rats

Contribute to diabetes-induced visual function decline and retinal inflammation

Activates p38/MAPK pathway, and promotes angiogenesis by interacting with WDR5 and MLL, which regulates ICAM-1 and VEGF transcription

[70, 139,140,141]

IPW

Upregulated in hypoxic ECs and the choroid of laser induced CNV in mice

Promote choroidal sprouting angiogenesis and laser-induced CNV

Represses miR-370 at the DLK1-DIO3 locus, which targets KDR and BMP-2

[82]

lncEGFL7OS

Enhances human angiogenesis

Interacts with MAX protein via to regulate EGFL7/miR-126 expression, therefore promoting MAPK and AKT pathway

[134]

MALAT1

Upregulated in HG-treated hRECs, OIR mouse model and diabetic patients

Promotes retinal vascularization, and contributes to DR vascular phenotypes

Acts as ceRNA for miR203a-3p, miR-205-5p, miR-124-3p, and miR-320 that target VEGF, HIF1 and EGR1, and promotes inflammation by elevating IL-1β, IL-6 and TNF-α levels.

[39, 48, 85,86,87,88,89,90,91]

MIAT

Upregulated by HG in cell lines, in diabetic rats and mice and in the plasma of DR patients

Contributes to diabetic-induced vascular phenotypes

Acts as ceRNA for mirR-150-5p that targets VEGF

[93,94,95,96]

NEAT1

Up- or down-regulated by HG-treated retinal cells, downregulated in STZ-treated mice but upregulated in the serum of DR patients

Promotes laser-induced CNV

Enhances angiogenesis by acting as ceRNA for miR-19-5p that targets TGB-βR2 and therefore enhancing VEGF-A expression; Inhibits resolving inflammation by inhibiting M2 macrophage polarization by acting ceRNA for miRNA-148a-3p that targets PTEN.

[100,101,102]

SNHG16

Upregulated in HG-treated ECs and the plasma of proliferative DR patients

Promotes angiogenesis in ECs but attenuates oxidative stress-induced angiogenesis

Acts ceRNA for multiple miRNAs

[123,124,125,126]

TUG1

Enhances retinal neovascularization and inflammation in mouse OIR model

Enhances angiogenesis by acting as ceRNA for miR-34a-5p and miR-299 that targets VEGF, miR-204-5p that targets JAK2, miR-145-5p that targets CCN1 and miR-29c-3p that targets PDGF-BB. It also promotes inflammation by elevating TNF-α, IL-1β and IL-6

[110, 111]

Vax2os1 and Vax2os2

Upregulated in the aqueous humour of wet AMD patients, and dynamically regulated in OIR model

Interacts with C1D and PATL2

[131, 132]