AUTHOR=Zerbini Gianpaolo , Maestroni Silvia , Leocani Letizia , Mosca Andrea , Godi Michela , Paleari Renata , Belvedere Arianna , Gabellini Daniela , Tirassa Paola , Castoldi Valerio , Viganò Ilaria , Galbiati Silvia , Turco Valentina , Lambiase Alessandro , Rama Paolo TITLE=Topical nerve growth factor prevents neurodegenerative and vascular stages of diabetic retinopathy JOURNAL=Frontiers in Pharmacology VOLUME=13 YEAR=2022 URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.1015522 DOI=10.3389/fphar.2022.1015522 ISSN=1663-9812 ABSTRACT=

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.