Animal Models of Diabetic Retinopathy: Summary and Comparison

Table 3

Comparison of the cellular and functional lesions in rat models of DR.

Animal model	Type of diabetes	Onset of hyperglycemia	Temporal morphological lesions in retina upon development of hyperglycemia		Temporal functional lesions in retina upon; development of hyperglycemia (ERG, SLO, fMRI)
			Cellular	Vascular
STZ injection	Type 1	Within 1 wk of injection	2 wk: increased apoptotic cells [136]; 1 mth: (i) Microglial cells hypertrophy [160]; (ii) Increased Müller cells and microglia cell number [160, 161]; (iii) Reduced astrocyte number [161]; (iv) Apoptosis of a few photoreceptor cells [162]; 6 wk: (i) Reduced astrocyte number [118]; (ii) Reduced astrocyte processes [118]; (iii) Reduced NeuN-positive ganglion cells in GCL [160]; (iv) Reduced cells in the ONL [163]; (v) Reduced total retinal thickness [163]; 4 mth: reduced NeuN-positive neurons in INL [160]	2 wk: BRB breakdown [161, 163]; 8 wk: increased adherent leukocytes [164]; 12 mth: arterial or venous capillaries basement membrane thickening [165]	2 wk: reduced b-wave amplitudes in ERG [166]; 4 wk: decreased positive scotopic threshold response in ERG [167]; 8 wk: decreased OPs in ERG [167]; 10 wk: reduced a-wave amplitudes in ERG [166]; 11 wk: (i) Reduced a-wave implicit time in ERG [168]; (ii) Delayed OPs in ERG [168]
Alloxan injection	Type 1	Within 1 wk of injection	12 mth: pericyte loss [169]	2 mth: (i) Neovascularization limited to the midperipheryregion[170]; (ii) Extravascular accumulation of monocytes and granulocytes [170]; 5 mth: (i) Neovascularization in the midperipheryregionand the center [170]; (ii) Capillary endothelial cells swelling [170]; 8 mth: retinal microvascular cell death [171]; 9 mth: neovascularization in all regions [170]; 12 mth: (i) Acellular capillaries [169]; (ii) Basement membrane thickening [169]
Galactose-fed	—	—	12 mth: pericyte loss [169]; 28 mth: (i) Gliosis [172]; (ii) Disruption of retinal layers [172]	6 mth: retinal microvascular cell death [171]; 12 mth: (i) Acellular capillaries [169]; (ii) Basement membrane thickening [169]; 28 mth: (i) Capillary dilation [172]; (ii) Microaneurysm formation in the IPL and the INL [172]
BB	Type 1	3-4 mth of age	4 mth: absence of infolding or derangement of the basal plasmalemma of the RPE [173]; 8 mth: (i) Reduced pericyte number [174]; (ii) Reduced pericyte to endothelial cell ratio [174]	2 mth: capillary dilation [175]; 4 mth: basement membrane thickening [175]; 8 mth: microinfarctions with areas of nonperfusion [175]
WBN/Kob	Type 2	9–12 mth of age	5 mth of age (prediabetic): reduced thickness of outer segments and ONL [176]; 2 mth: (i) Reduced thickness of total retinal layer, OPL [176]; (ii) Visual cells disappeared [176]	1 mth: capillaries clustered into small tortuous knots [177]; 5 mth: capillary basement membrane thickening [176]; 6 mth: (i) Increased capillary loop [177]; (ii) Reduced number of capillary [177]; 12 mth: (i) Increased fibrovascular element proliferation in the vitreous [178]; (ii) Increased intraretinal neovascularization [178]; (iii) Increased hyalinization of intraretinal vessels [178]
ZDF	Type 2	6-7 wk of age	6 mth: (i) Increased apoptotic pericytes [179]; (ii) Increased pericyte ghosts [179]	5 mth: (i) Capillary basement membrane thickening [180, 181]; (ii) Increased capillary cell nuclear density [180, 181]; 6 mth: (i) Increased apoptotic endothelial cells [179]; (ii) Acellular capillaries [179]
OLETF	Type 2	5 mth of age	9 mth: (i) Damaged endothelial cells [182]; (ii) Reduced ratio of pericyte area to the total capillary cross-sectional area [183]; 14 mth: (i) Decreased thickness of INL [182]; (ii) Decreased thickness of photoreceptor layer [182]; (iii) RPE decreased in height [182]; (iv) Basal infoldings were poorly developed [182]	6 wk: leukostasis [184]; 9 mth: (i) Capillary basement membrane thickening [182, 183]; (ii) Caliber irregularity [183, 185]; (iii) Narrowing of arteries [185]; 9–12 mth: (i) Tortuosity [182, 183, 185]; (ii) Microaneurysms [182, 183, 185]; (iii) Loop formation in capillary [182, 183, 185]
GK	Type 2, nonobese	4–6 wk of age	7 mth: increased endothelial/pericyte ratio [186]	1 mth: (i) Reduced retinal segmental blood flows [186]; (ii) Increased retinal mean circulation time [186]; 3 mth: increased BRB permeability [187]
SDT	Type 2, nonobese	5 mth of age	20 wk: increased apoptotic cells in the GCL and the INL [188]; 48 wk: distortion of retina and protruded optic disc [189]; 50 wk: tractional retinal detachment with fibrous proliferation [190]; 15 mth: (i) Proliferative retinopathy without vascular nonperfusion (53% of rats) [191]; (ii) Traction retinal folds [191]	24 wk: leukostasis [192]; 48 wk: leakage of fluorescein around the optic disc [189]	4 wk: delayed peak latency of the ΣOPs in ERG [189]; 24 wk: (i) Reduced a-wave, b-wave, and OPs amplitudes in ERG [193]; (ii) Prolonged implicit times in a-wave, b-wave, and OPs in ERG [193]
OIR	—	—	P18: (i) Reduced thickness in INL, IPL, and total retinal layer [194]; (ii) Müller cell gliosis in peripheral region [194]; (iii) Reduced astrocyte number [195]; (iv) Impaired pericyte endothelial interactions [195]; (v) Disorganized and thinning of the outer segment [196]	P18: (i) Intravitreal neovascularization [195]; (ii) Underdevelopment of the outer vascular plexus [195]; (iii) Increased tortuosity in arterioles [197]	P16: reduced a-wave and b-wave amplitudes in ERG [197]

The observations reported at a particular time point, which was chosen by the authors, may not totally reflect the sequential processes.