Enhanced survival of melanopsin-expressing ganglion cells and the non-image-forming visual system after acute retinal ischemia

DORFMAN D; GONZÁLEZ FLEITAS MF; ARANDA ML; SANDE PH; ROSENSTEIN RE

Congreso; Society for Neuroscience Annual Meeting 2014; 2014

Society for Neuroscience

Retinal ischemia/reperfusion injury is an important cause of visual impairment. The loss of retinal ganglion cells (RGCs) is a key sign of retinal ischemia. A subset of RGCs expressing the photopigment melanopsin (mRGCs) regulates non-image-forming visual functions such as the pupillary light reflex (PLR) and circadian rhythms. We studied the effect of retinal ischemia on melanopsin expressing RGCs and the non-image-forming visual system. For this purpose, ischemia was induced in male Wistar rats by increasing intraocular pressure (120 mm Hg for 40 min). Retinal function (electroretinogram (ERG)), the number of Brn3a(+) and melanopsin(+) RGC (immunohistochemistry), Brn3a and melanopsin levels (Western Blot), and the consensual pupil light reflex (PRL) (after 10-s light flash) were examined. Anterograde transport was assessed after an intravitreal injection of cholera toxin β-subunit, and circadian rhythms of general locomotor activity were registered in cages equipped with infrared detectors of motion. After 4 weeks of ischemia, clear alterations in the visual function (ERG)and retinal histology were observed. Concomitantly with a significant decrease in the number of Brn3a(+) RGC and in Brn3a levels, no differences in the number of melanopsin(+) cells, and melanopsin levels were observed between non-ischemic and ischemic retinas.Ischemia decreased anterograde transport to the superior colliculus and lateral geniculate nucleus, whereas the anterograde transport to the suprachiasmatic nucleus and the olivary pretectal nucleus remained unaffected. At high light intensity, consensual PLR was conserved in ischemic eyes, whereas at low light intensity, a decrease in pupil constriction was observed in intact eyes contralateral to ischemic eyes. Animals with ischemia in both eyes showed a conserved locomotor activity pattern and a photoentrainment rate which did not differ from control animals. The present results indicate a marked preservation of a unique subtype of RGCs, mRGCs, which was functionally and structurally protected even after an extensive retinal damage such as that observed at 4 weeks after ischemia.