期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 20, 期 12, 页码 -出版社
MDPI
DOI: 10.3390/ijms20123012
关键词
NMDA; excitotoxicity; glaucoma; melanopsin-RGCs; intrinsically photosensitive-RGCs; Brn3a(+)RGCs; adult albino rat; retina; SD-OCT
资金
- Fundacion Seneca
- Agencia de Ciencia y Tecnologia Region de Murcia [19881/GERM/15]
- Spanish Ministry of Economy and Competitiveness, Instituto de Salud Carlos III, Fondo Europeo de Desarrollo Regional una manera de hacer Europa [SAF2015-67643-P, PI16/00380, RD16/0008/0026, RD16/0008/0016]
We studied short- and long-term effects of intravitreal injection of N-methyl-d-aspartate (NMDA) on melanopsin-containing (m(+)) and non-melanopsin-containing (Brn3a(+)) retinal ganglion cells (RGCs). In adult SD-rats, the left eye received a single intravitreal injection of 5 mu L of 100nM NMDA. At 3 and 15 months, retinal thickness was measured in vivo using Spectral Domain-Optical Coherence Tomography (SD-OCT). Ex vivo analyses were done at 3, 7, or 14 days or 15 months after damage. Whole-mounted retinas were immunolabelled for brain-specific homeobox/POU domain protein 3A (Brn3a) and melanopsin (m), the total number of Brn3a(+)RGCs and m(+)RGCs were quantified, and their topography represented. In control retinas, the mean total numbers of Brn3a(+)RGCs and m(+)RGCs were 78,903 +/- 3572 and 2358 +/- 144 (mean +/- SD; n = 10), respectively. In the NMDA injected retinas, Brn3a(+)RGCs numbers diminished to 49%, 28%, 24%, and 19%, at 3, 7, 14 days, and 15 months, respectively. There was no further loss between 7 days and 15 months. The number of immunoidentified m(+)RGCs decreased significantly at 3 days, recovered between 3 and 7 days, and were back to normal thereafter. OCT measurements revealed a significant thinning of the left retinas at 3 and 15 months. Intravitreal injections of NMDA induced within a week a rapid loss of 72% of Brn3a(+)RGCs, a transient downregulation of melanopsin expression (but not m(+)RGC death), and a thinning of the inner retinal layers.
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