Neuroprotection by α2-Adrenergic Receptor Stimulation after Excitotoxic Retinal Injury: A Study of the Total Population of Retinal Ganglion Cells and Their Distribution in the Chicken Retina.
We have studied the effect of α2-adrenergic receptor stimulation on the total excitotoxically injured chicken retinal ganglion cell population. N-methyl-D-aspartate (NMDA) was intraocularly injected at embryonic day 18 and Brn3a positive retinal ganglion cells (Brn3a+ RGCs) were counted in flat-mounted retinas using automated routines. The number and distribution of the Brn3a+ RGCs were analyzed in series of normal retinas from embryonic day 8 to post-hatch day 11 retinas and in retinas 7 or 14 days post NMDA lesion. The total number of Brn3a+ RGCs in the post-hatch retina was approximately 1.9x106 with a density of approximately 9.2x103 cells/mm2. The isodensity maps of normal retina showed that the density decreased with age as the retinal size increased. In contrast to previous studies, we did not find any specific region with increased RGC density, rather the Brn3a+ RGCs were homogeneously distributed over the central retina with decreasing density in the periphery and in the region of the pecten oculli. Injection of 5-10 μg NMDA caused 30-50% loss of Brn3a+ cells and the loss was more severe in the dorsal than in the ventral retina. Pretreatment with brimonidine reduced the loss of Brn3a+ cells both 7 and 14 days post lesion and the protective effect was higher in the dorsal than in the ventral retina. We conclude that α2-adrenergic receptor stimulation reduced the impact of the excitotoxic injury in chicken similarly to what has been shown in mammals. Furthermore, the data show that the RGCs are evenly distributed over in the retina, which challenges previous results that indicate the presence of specific high RGC-density regions of the chicken retina.
Department of Neuroscience, Uppsala University, Box 593, 751 24 Uppsala, Sweden.|Instituto Murciano de Investigación Biosanitaria Hospital Virgen de la Arrixaca (IMIB-Virgen de la Arrixaca) and Departamento de Oftalmología, Facultad de Medicina, Universidad de Murcia, Murcia, Spain.
Caridad
C
Galindo-Romero
Department of Neuroscience, Uppsala University, Box 593, 751 24 Uppsala, Sweden.
Mohammad
M
Harun-Or-Rashid
Instituto Murciano de Investigación Biosanitaria Hospital Virgen de la Arrixaca (IMIB-Virgen de la Arrixaca) and Departamento de Oftalmología, Facultad de Medicina, Universidad de Murcia, Murcia, Spain.
Manuel
M
Jiménez-López
Instituto Murciano de Investigación Biosanitaria Hospital Virgen de la Arrixaca (IMIB-Virgen de la Arrixaca) and Departamento de Oftalmología, Facultad de Medicina, Universidad de Murcia, Murcia, Spain.
Manuel
M
Vidal-Sanz
Instituto Murciano de Investigación Biosanitaria Hospital Virgen de la Arrixaca (IMIB-Virgen de la Arrixaca) and Departamento de Oftalmología, Facultad de Medicina, Universidad de Murcia, Murcia, Spain.
Marta
M
Agudo-Barriuso
Department of Neuroscience, Uppsala University, Box 593, 751 24 Uppsala, Sweden.
Finn
http://orcid.org/0000-0001-7552-187X
F
Hallböök
D000818:Animals; D002642:Chick Embryo; D002645:Chickens; D016202:N-Methylaspartate / Q000008:administration & dosage / Q000494:pharmacology*; D000066829:Neuroprotection / Q000502:physiology; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism*; D012160:Retina / Q000166:cytology* / Q000187:drug effects* / Q000196:embryology; D012164:Retinal Diseases / Q000378:metabolism* / Q000473:pathology*; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000378:metabolism; D050819:Transcription Factor Brn-3A / Q000378:metabolism
D018341:Receptors, Adrenergic, alpha-2; D050819:Transcription Factor Brn-3A; D016202:N-Methylaspartate