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] |
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|
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| 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] |
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| |||||
| 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.