Table 3.

An overview of preclinical research targeting vasodegeneration and neurodegeneration in DR.

Reference	Vector type	Promoter	Transgene	Target	Vascular protection	Neuronal protection
Dominguez et al. [145]	AAV	CBA	ACE2	RAAS system	Yes	n/a
Vacca et al. [146]	ShH10	CAG	Dp71	Muller cells	Yes	n/a
Zhang et al. [147]	AAV2	CAG	MnSOD	Superoxide	Yes	n/a
Xu et al. [148]	AAV2	CMV	EPO	EPO receptor	Yes	Yes
Hu et al. [149]	TransIT-TKO	U6	CTGF shRNA	CTGF	Yes	n/a
Adhi et al. [144]	AAV2/8	CAG	sCD59	MAC	Yes	Yes
Verma et al. [41]	AAV2	CAG	ACE2 or Ang(1–7)	RAAS	Yes	n/a
Gong et al. [150]	AAV	CBA	BDNF	Neuronal cells	n/a	Yes
Ramirez et al. [151]	AAV2	CAG	Vasoinhibin, PRL, sFLT-1	VEGF signaling	Yes	n/a
Shyong et al. [152]	AAV	CMV	Angiostatin	Endothelium	Yes	n/a

CAD180: Calrectulin anti-angiogenic domain; CAD112: CAD-like peptide 112; ShH10: a Muller cell-specific variant of the AAV vector; ACE2: angiotensin-converting enzyme 2; EPO: erythropoietin; CTGF: connective tissue growth factor; CAG: cytomegalovirus early enhancer; CBA: chicken-β actin promoter; MnSOD: manganese superoxide dismutase; U6: human RNA polymerase III promoter; MAC: membrane attack complex; BDNF: brain-derived neurotrophic factor; PRL: proteolytic cleavages of prolactin; ACE2: angiotensin-converting enzyme 2; sFLT-1: soluble FLT1 receptor (aflibercept). Adapted from Pharmacology & Therapeutics, Vol 173, Wang et al., Gene therapy for diabetic retinopathy: Are we ready to make the leap from bench to bedside?, Copyright 2017, with permission from Elsevier [7].