Diabetes has no additional impact on retinal ganglion cell loss in a mouse model of spontaneous glaucoma.

PURPOSE: There is no valid medical treatment for diabetic retinopathy mostly because its pathogenesis remains largely unknown. Early stages of diabetic retinopathy, just like glaucoma, are characterized by the loss of retinal ganglion cells. Whether the two diseases may share a similar pathogenic background is unknown. METHODS: To clarify this issue the thickness of retinal nerve fiber layer was studied in vivo by optical coherence tomography in 10 Ins2Akita (diabetic) and 10 C57BL/6J (control) mice. The number of retinal ganglion cells and retina's surface covered by neurofilaments were quantified ex vivo in 12 normoglycemic DBA/2J (glaucoma) and 11 diabetic (alloxan-induced) DBA/2J mice (glaucoma + diabetes). RESULTS: At 16 weeks of age retinal nerve fiber layer was significantly thinner in Ins2Akita mice confirming the neurodegenerative impact of diabetes. Number of retinal ganglion cells and retina's surface covered by neurofilaments were similar in normoglycemic and diabetic DBA/2J mice with the exception of the superior quadrant where the number of retinal ganglion cells was increased in animals with glaucoma + diabetes. CONCLUSIONS: In presence of glaucoma, diabetes is unable to induce further retinal ganglion cells loss. The hypothesis that the mechanism leading to retinal ganglion cells loss may be shared by the two diseases cannot be ruled out. Whether early diabetes-driven retinal neurodegeneration could be prevented by neuroprotective treatment proven to be effective in case of glaucoma, remains to be clarified.

Topical nerve growth factor prevents neurodegenerative and vascular stages of diabetic retinopathy.

Specific and effective preventive treatment for diabetic retinopathy (DR) is presently unavailable, mostly because the early stages of the complication have been, until recently, poorly understood. The recent demonstration that the vascular phase of DR is preceded and possibly caused by the neurodegeneration of retinal ganglion cells suggests that DR could, at least theoretically, be prevented through an early neuroprotective approach. The aims of our study were to clarify the natural history of diabetes-driven retinal neurodegeneration and to verify the possibility to prevent DR using topical nerve growth factor (NGF). The results of the study show that retinal neurodegeneration, characterized by the loss of retinal ganglion cells represents a relatively early phenomenon of diabetes (between 5 and 16 weeks of age), which tends to be self-limiting in the long run. Neurodegeneration is followed by the development of DR-related vascular dysfunctions, as confirmed by the development of acellular capillaries and the loss of retinal pericytes. Both retinal neurodegeneration and subsequent vascular dysfunction can be successfully prevented by topical NGF administration. These findings suggest that: 1) The first stage of DR consists in a self-limiting retinal neurodegeneration 2) The demonstrated effectiveness of topical NGF in the prevention of DR could be rapidly translated into clinical practice.