Diabetes exacerbates the intraocular pressure-independent retinal ganglion cells degeneration in the DBA/2J model of glaucoma

Rosario Amato, Francesca Lazzara, Tsung Han Chou, Giovanni Luca Romano, Maurizio Cammalleri, Massimo Dal Monte, Giovanni Casini, Vittorio Porciatti

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

PURPOSE. Glaucoma is a multifactorial disease, causing retinal ganglion cells (RGCs) and optic nerve degeneration. The role of diabetes as a risk factor for glaucoma has been postulated but still not unequivocally demonstrated. The purpose of this study is to clarify the effect of diabetes in the early progression of glaucomatous RGC dysfunction preceding intraocular pressure (IOP) elevation, using the DBA/2J mouse (D2) model of glaucoma. METHODS. D2 mice were injected with streptozotocin (STZ) obtaining a combined model of diabetes and glaucoma (D2 + STZ). D2 and D2 + STZ mice were monitored for weight, glycemia, and IOP from 3.5 to 6 months of age. In addition, the activity of RGC and outer retina were assessed using pattern electroretinogram (PERG) and flash electroretinogram (FERG), respectively. At the end point, RGC density and astrogliosis were evaluated in flat mounted retinas. In addition, Müller cell reactivity was evaluated in retinal cross-sections. Finally, the expression of inflammation and oxidative stress markers were analyzed. RESULTS. IOP was not influenced by time or diabetes. In contrast, RGC activity resulted progressively decreased in the D2 group independently from IOP elevation and outer retinal dysfunction. Diabetes exacerbated RGC dysfunction, which resulted independent from variation in IOP and outer retinal activity. Diabetic retinas displayed decreased RGC density and increased glial reactivity given by an increment in oxidative stress and inflammation. CONCLUSIONS. Diabetes can act as an IOP-independent risk factor for the early progression of glaucoma promoting oxidative stress and inflammation-mediated RGC dysfunction, glial reactivity, and cellular death.

Original languageEnglish (US)
Article number9
JournalInvestigative Ophthalmology and Visual Science
Volume62
Issue number9
DOIs
StatePublished - Jul 2021

Keywords

  • Flash electroretinogram
  • Inflammation
  • Oxidative stress
  • Pattern electroretinogram

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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