Changes in retinal neuronal populations in the DBA/2J mouse.
DBA/2J (D2) mice develop a form of progressive pigmentary glaucoma with increasing age. We have compared retinal cell populations of D2 mice with those in control C57BL/6J mice to provide information on retinal histopathology in the D2 mouse. The D2 mouse retina is characterized by a reduction in retinal thickness caused mainly by a thinning of the inner retinal layers. Immunocytochemical staining for specific inner retinal neuronal markers, viz., calbindin for horizontal cells; protein kinase C (PKC) and recoverin for bipolar cells, glycine, gamma-aminobutyric acid (GABA), choline acetyltransferase (ChAT), and nitric oxide synthase (NOS) for amacrine cells, and osteopontin (OPN) for ganglion cells, was performed to detect preferentially affected neurons in the D2 mouse retina. Calbindin, PKC, and recoverin immunoreactivities were not significantly altered. Amacrine cells immunoreactive for GABA, ChAT, and OPN were markedly decreased in number, whereas NOS-immunoreactive amacrine cells increased in number. However, no changes were observed in the population of glycine-immunoreactive amacrine cells. These findings indicate a significant loss of retinal ganglion and some amacrine cells, whereas glycinergic amacrine cells, horizontal, and bipolar cells are almost unaffected in the D2 mouse. The reduction in amacrine cells appears to be attributable to a loss of GABAergic and particularly cholinergic amacrine cells. The increase in nitrergic neurons with the consequent increase in NOS and NO may be important in the changes in the retinal organization that lead to glaucomain D2 mice. Thus, the D2 mouse retina represents a useful model for studying the pathogenesis of glaucoma and mechanisms of retinal neuronal death and for evaluating neuroprotection strategies.
Moon
Jung-Il
JI
Department of Ophthalmology, College of Medicine, The Catholic University of Korea, Seoul, 137-701, Korea.
Kim
In-Beom
IB
Gwon
Jae-Sung
JS
Park
Myoung-Hee
MH
Kang
Tae-Hoon
TH
Lim
Eun-Jin
EJ
Choi
Kyu-Ryong
KR
Chun
Myung-Hoon
MH
D025042:Amacrine Cells / Q000166:cytology* / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D019084:Fluorescent Antibody Technique, Indirect; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D012160:Retina / Q000166:cytology* / Q000378:metabolism; D012165:Retinal Ganglion Cells / Q000166:cytology* / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D015415:Biomarkers; D005680:gamma-Aminobutyric Acid