Neuronal nitric oxide synthase (nNOS) positive retinal amacrine cells are altered in the DBA/2NNia mouse, a murine model for angle-closure glaucoma.
OBJECTIVE
To characterize retinal amacrine cell changes in eyes of DBA/2NNia (DBA) mice that develop an inherited angle-closure glaucoma.


METHODS
DBA and non-glaucomatous C57BL/6J mice of different age groups (2 to 23 months of age) were studied and compared. Morphologic investigations included NADPH-diaphorase staining of retinal whole mounts and fluorescence immunohistochemistry of cryosections with antibodies against neuronal nitric oxide synthase (nNOS), tyrosin hydroxylase (TH), gamma aminobutyric acid (GABA), and vesicular acetylcholine transporter (VAChT).


RESULTS
Immunohistochemistry of amacrine cell subpopulations in the retinae of DBA mice revealed no significant staining differences in the two mouse strains at all ages using antibodies against TH, GABA, and VAChT. However, staining with nNOS and NADPH diaphorase revealed significant differences between the DBA strain and the C57BL/6J mice. With the onset of elevated IOP and glaucoma beginning at around 6 months in the DBA mice, the total number of NOS positive amacrine cells continuously decreased from 1000 cells at 6 months of age down to 480 cells in animals older than 20 months of age, but did not decline in age-matched C57 mouse retinas.


CONCLUSIONS
We previously described a parafoveal loss of nNOS positive amacrine cells in the monkey glaucoma model. The fact that there is also a significant decrease of nNOS amacrine cells in the glaucomatous mouse eye indicates a specific response of nNOS positive amacrine cells in glaucomatous retinopathy.
May
Christian Albrecht
CA
Department of Anatomy, Friedrich Alexander University, Erlangen, Germany. Albrecht.May@anatomie2.med
Mittag
Thom
T
D025042:Amacrine Cells / Q000201:enzymology* / Q000378:metabolism; D000818:Animals; D004195:Disease Models, Animal; D015812:Glaucoma, Angle-Closure / Q000201:enzymology* / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D026901:Membrane Transport Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA / Q000235:genetics*; D009252:NADPH Dehydrogenase / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I; D012160:Retina / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D050494:Vesicular Acetylcholine Transport Proteins; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D026901:Membrane Transport Proteins; C493460:Slc18a3 protein, mouse; D050494:Vesicular Acetylcholine Transport Proteins; D005680:gamma-Aminobutyric Acid; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496321:Nos1 protein, mouse; D014446:Tyrosine 3-Monooxygenase; D009252:NADPH Dehydrogenase