Significant Retinal Capillary Basement Membrane Thickening in Hyperglycemic and Normoglycemic Diabetic-prone (DP) BB Wistar Rats

Abstract

The diabetic-prone BioBreeding Wistar (BB/DP) rat is an autoimmune model of insulin-dependent diabetes mellitus. Approximately 90% of the animals (BB/DPh) are hyperglycemic by 90-120 days of age, while the remaining ~10% (BB/DPn) and diabetes-resistant rats (BB/DR) are normoglycemic for life. The transmission electron microscope data from this study demonstrate expected significant age- and diabetes-related increases in retinal capillary basement membrane (RCBM) widths in (BB/DPh) rats relative to BB/DR animals. However, the data show, for the first time, an unexpected significant RCBM thickening in (BB/DPn) rats compared to BB/DR animals at 6 months and 1 year post-onset of hyperglycemia.

Diabetic Basement Membrane Thickening Does Not Occur in Myocardial Capillaries of Transgenic Mice When Metallothionein is Overexpressed in Cardiac Myocytes

“…Distributions of true myocardial CBM thickness derived from orthogonal intercepts on sets of 20 randomized transmission electron micrographs were analyzed as previously described (Carlson et al, , Greenwood et al, , Teiken et al, , Carlson et al, in press). Two‐way analysis of variance (ANOVA) and a Holm–Sidak post hoc multiple comparison test were used to compare CBM thickness for each mouse genotype.…”

Animal Models of Diabetic Retinopathy

“…45,46 Similarly, spontaneous diabetic BioBreeding rats demonstrate pericyte degeneration, BM thickening and areas of non-perfusion. 47,48 The spontaneous diabetic torii (SDT) rat has several distinctive features. It is the only strain in which certain individuals develop symptoms of severe DR, including retinal and iris neovascularization, and tractional retinal detachment with fibrous proliferation.…”

Animal Models of Diabetic Retinopathy (Part 2)

“…of acellular capillaries [12] (18 mo + [10]) Capillary BM thickening [12] • 2 mo + : neovascularization in midperiphery region [11] • 5 mo + : neovascularization in center and mid-periphery regions [11] • 9 mo + : neovascularization in all regions [11] Experimental [12] (23 mo + )*^ [13] Increased no. of acellular capillaries [12] (23 mo + )*^ [13] Capillary BM thickening [12] (23 mo + )*^ [13] (28 mo + )^ [14] • 24 mo + : dilated, hypercellular vessels*^ [13] IRMAs* [13] • 28 mo + : disrupted retinal layers^ [14] Gliosis^ [14] Capillary dilatation^ [14] Microaneurysms (OPL, INL)^ [14] Increased number of endothelial cells^ [14] *50% galactose diet; ^30% galactose diet BB rat 1 60-120 days (90% hyperglycemic by 90-120 days) [15] • 6 mo: increased retinal capillary BM thickness [15,18] • 7.7 ± 1.1 mo: reduced and deranged basal infoldings of the RPE basal plasmalemma [16] • 8 mo + : decreased pericyte/endothelial cell ratio [17] Decreased number of pericytes [17] Microinfarctions with nonperfused areas [19] Animal Models of Diabetic Retinopathy (Part 2) http://dx.doi.org/10.5772/intechopen.70589 [21] Complete photoreceptor cell nuclei and ONL loss ( [21,22], 169)…”

“…Long-term galactosemia of 28 months further resulted in gliosis, displacement or disruption of retinal layers, an increase in the number of endothelial cells, and microaneurysm formation in the outer plexiform layer (OPL) and inner nuclear layer (INL) [14]. [15]. Existing reports have demonstrated reduced and deranged basal infoldings of the retinal pigment epithelium (RPE) basal plasmalemma [16], pericyte loss, reduced pericyte to endothelial cell ratios [17], capillary BM thickening [15,18], and microinfarctions [19].…”

“…[15]. Existing reports have demonstrated reduced and deranged basal infoldings of the retinal pigment epithelium (RPE) basal plasmalemma [16], pericyte loss, reduced pericyte to endothelial cell ratios [17], capillary BM thickening [15,18], and microinfarctions [19]. Microaneurysm formation and neovascularization were absent even after 11 months of diabetes [19].…”