Diabetes exacerbates the early RGCs loss of function in the DBA/2J inherited mouse model of Glaucoma

Abstract

AbstractPurposeGlaucoma is a multifactorial disease that progressively determines the dysfunction and the subsequent death of retinal ganglion cells (RGCs), depending or not by the intraocular pressure (IOP) elevation. The possible influence of diabetes as a risk and/or exacerbating factor for glaucoma has been postulated, but the relationship between diabetes and glaucoma remains controversial. The purpose of this study is to clarify the effect of diabetes in the early progression of glaucoma during the RGCs dysfunction stage preceding the IOP elevation and the cell death.MethodsDBA/2J glaucomatous mice were injected with streptozotocin (STZ) to obtain a combined model of diabetes and glaucoma. In addition, non‐treated DBA/2J mice and STZ‐injected C57BL/6J were analyzed respectively as glaucomatous and diabetic only controls. RGCs and outer retina activities were evaluated performing respectively pattern electroretinogram (PERG) and flash electroretinogram (FERG) from 4 to 6 month of age. Additionally, IOP and glycaemia were followed up to monitor the progression of the disease.ResultsAs expected, non‐treated DBA/2J mice didn’t show any elevation of IOP nor alteration of FERG response during this time window. However, this group showed an age‐dependent worsening of the amplitude and the latency related to the PERG response. C57BL/6J mice treated with STZ showed an IOP‐independent decrease in PERG response preceding alterations of FERG. Interestingly, hyperglycemia determined the exacerbation of the PERG response in STZ‐treated DBA/2J compared to both diabetic and glaucomatous only groups starting from the very beginning of the diabetic condition independently from both IOP and FERG changings.ConclusionOur results show that diabetes act as an exacerbating factor for the progression of glaucoma. Indeed, hyperglycemic condition act as a further stressor which leads to a quicker loss of RGCs function and cell death.