Retinal neurodegeneration in the DBA/2J mouse – a model for ocular hypertension

Abstract

Abstract: : Purpose: Mice of the DBA/2J strain spontaneously develop complex ocular abnormalities including glaucomatous loss of retinal ganglion cells (RGC). In the present study clinical and ultrastructural features of retinal neurodegeneration in DBA/2J mice of different age are described. Methods: Clinical examinations: Anterior segments were examined with a slit–lamp biomicroscope. Photographs were taken using a fundus camera. Fluorescein fundus angiography (FFA) was performed on mice between 6 and 11 months of age. Fundus fluorescent images were obtained with a scanning laser ophthalmoscope using argon laser (488 nm, 1mW) as an exciter, and were recorded on S–VHS videotape. Electron microscopy: Retinas were collected from DBA/2J mice 3, 6, 8 and 11 months old. C57BL6 mice were used as age–matched controls. Results: By 3 months, RGC apoptosis of ganglion cells was observed. The occurrence of apoptotic ganglion cells peaked at the age of 6 months. Past this age necrosis appeared to be the prevailing form of cell death. Müller glia activation increased with age, but there were no signs of leukocyte infiltration. At 8 and 11 months, signs of neoangiogenesis were found both at the ultrastructural level and in clinical examinations. Photoreceptor cells were not affected at any age. Conclusions:Our observations suggest that retinal degeneration in the DBA/2J mice does not involve recruitment of blood–borne inflammatory/phagocytizing cells, and that apoptosis is gradually replaced by necrosis as the predominant pathway of the RGC death. Retinal degeneration in DBA/2J mice 3–11 months old partially resembles clinical features of human pigment dispersion syndrome and pigmentary glaucoma. However, neovasculogenesis and myelin–like bodies are observed during aging. Therefore, the DBA/2J model requires judicious interpretation as a glaucoma model.

Keywords: ganglion cells • retina: proximal (bipolar, amacrine, and ganglion cells) • neuro–ophthalmology: optic nerve