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Updated: Aug 15, 2026
An Assay to Detect Protection of the Retinal Vasculature from Diabetes-Related Death in Mice
Published on: January 12, 2024
Vascular damage in a mouse model of diabetic retinopathy: relation to neuronal and glial changes
Rachel A Feit-Leichman1, Reiko Kinouchi, Masumi Takeda
1Schepens Eye Research Institute and Department of Ophthalmology, Harvard Medical School, Boston, MA 02114, USA.
Purpose:
Lack of information about the development of diabetic retinopathy in mice has greatly hindered the use of genetic mouse models for the study of disease mechanisms and the development of therapeutic strategies. The objective of this study was to characterize the occurrence and pathologic progression of diabetic retinopathy in C57Bl/6J mice.
Methods:
Diabetes was induced with five consecutive injections of streptozotocin (STZ). The retinas were collected at different time points (2 weeks to 22 months) after the induction of diabetes and examined by using molecular, histologic, and immunohistochemical techniques and morphometric analysis.
Results:
There was transient induction of cell apoptosis and caspase-3 activation in retinal neurons of C57Bl/6 mice within days of diabetes induction. Glial fibrillary acidic protein (GFAP), a marker of glial activation, likewise was transiently upregulated, seemingly in astrocytes but not in Müller cells. These abnormalities quickly returned to normal; ultimately, no detectable loss of retinal ganglion cells (RGCs) was noted by any of three independent methods (number of cells in ganglion cell layer of retinal cross-sections, retrograde labeling of retinal ganglion cells with fluorescent dye, or TUNEL staining) after up to a 1-year duration of diabetes. Despite this apparent lack of evidence for progressive damage in neurons and glial cells, diabetic mice developed vascular disease characteristic of the early stage of diabetic retinopathy beginning at 6 months after the onset of disease. The vascular damage-formation of acellular capillaries and pericyte ghosts-continued to increase through the 18 months examined.
Conclusions:
Diabetic C57Bl/6J mice develop capillary lesion that are characteristic of the early stages of diabetic retinopathy in patients. The data suggest that diabetes-induced degeneration of retinal capillaries can develop independent of neuronal loss or chronic GFAP upregulation in glial cells.
Insights
Diabetic C57Bl/6J mice develop early diabetic retinopathy vascular lesions, including acellular capillaries and pericyte ghosts, independent of neuronal loss or glial cell activation. This study characterizes the progression of these early-stage changes.
Area of Science:
- Ophthalmology
- Diabetology
- Pathology
Background:
- Diabetic retinopathy (DR) is a leading cause of vision loss.
- Genetic mouse models are crucial for studying DR mechanisms and therapies.
- Limited information exists on DR development in C57Bl/6J mice.
Purpose of the Study:
- To characterize the occurrence and pathological progression of diabetic retinopathy in C57Bl/6J mice.
- To establish a reliable mouse model for early-stage DR research.
Main Methods:
- Diabetes was induced using streptozotocin (STZ).
- Retinas were analyzed using molecular, histologic, immunohistochemical, and morphometric techniques at various time points (2 weeks to 22 months).
- Apoptosis, glial activation (GFAP), retinal ganglion cell (RGC) counts, and vascular changes were assessed.
Main Results:
- Transient retinal neuron apoptosis and caspase-3 activation occurred within days of STZ injection.
- Glial fibrillary acidic protein (GFAP) was transiently upregulated in astrocytes.
- No significant retinal ganglion cell loss was detected up to 1 year of diabetes.
- Early-stage DR vascular lesions, including acellular capillaries and pericyte ghosts, emerged at 6 months and progressed over 18 months.
Conclusions:
- Diabetic C57Bl/6J mice develop capillary lesions characteristic of early human DR.
- Diabetes-induced retinal capillary degeneration can occur independently of neuronal loss or chronic glial activation.
- This model is suitable for studying early DR pathogenesis and testing therapeutic strategies.
