Optimization of an Ischemic Retinopathy Mouse Model and the Consequences of Hypoxia in a Time-Dependent Manner

Int J Mol Sci. 2024 Jul 23;25(15):8008. doi: 10.3390/ijms25158008.

Abstract

The retina is one of the highest metabolically active tissues with a high oxygen consumption, so insufficient blood supply leads to visual impairment. The incidence of related conditions is increasing; however, no effective treatment without side effects is available. Furthermore, the pathomechanism of these diseases is not fully understood. Our aim was to develop an optimal ischemic retinopathy mouse model to investigate the retinal damage in a time-dependent manner. Retinal ischemia was induced by bilateral common carotid artery occlusion (BCCAO) for 10, 13, 15 or 20 min, or by right permanent unilateral common carotid artery occlusion (UCCAO). Optical coherence tomography was used to follow the changes in retinal thickness 3, 7, 14, 21 and 28 days after surgery. The number of ganglion cells was evaluated in the central and peripheral regions on whole-mount retina preparations. Expression of glial fibrillary acidic protein (GFAP) was analyzed with immunohistochemistry and Western blot. Retinal degeneration and ganglion cell loss was observed in multiple groups. Our results suggest that the 20 min BCCAO is a good model to investigate the consequences of ischemia and reperfusion in the retina in a time-dependent manner, while the UCCAO causes more severe damage in a short time, so it can be used for testing new drugs.

Keywords: hypoxia; ischemia; retina.

MeSH terms

  • Animals
  • Disease Models, Animal*
  • Glial Fibrillary Acidic Protein* / metabolism
  • Hypoxia* / metabolism
  • Ischemia* / metabolism
  • Ischemia* / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Retina* / metabolism
  • Retina* / pathology
  • Retinal Diseases / etiology
  • Retinal Diseases / metabolism
  • Retinal Diseases / pathology
  • Retinal Ganglion Cells / metabolism
  • Retinal Ganglion Cells / pathology
  • Time Factors
  • Tomography, Optical Coherence*

Substances

  • Glial Fibrillary Acidic Protein

Grants and funding

This research work was conducted with the support of the National Academy of Scientist Education Program of the National Biomedical Foundation under the sponsorship of the Hungarian Ministry of Culture and Innovation (FEIF/646-4/2021- ITM_SZERZ). National Research, Development and Innovation Fund FK129190, K135457; PTE AOK-TANDEM, National Brain Research Program NAP3. HUN-REN TKI14016; and Higher Education Institutional Excellence Programme of the Ministry of Human Capacities in Hungary: TKP2021-EGA-16.