Decrease of cone opsin mRNA in experimental ocular hypertension.
OBJECTIVE
This study was designed to test the hypothesis that photoreceptors are adversely affected in glaucoma. As a measure of this effect, we examined the levels of rod opsin, and red/green and blue cone opsin mRNAs in monkeys with experimental ocular hypertension and glaucoma and in human eyes from donors with diagnosed glaucoma.


METHODS
Experimental ocular hypertension was induced in one eye of 19 cynomolgous and 2 rhesus monkeys by laser ablation of the trabecular meshwork. In 15 monkeys, the elevated IOP was reduced by trabeculectomy. When the animals had experienced prolonged elevations of IOP (128 to 260 days), they were killed and the eyes enucleated. Fresh retinal tissue from the macula, inferotemporal retina (mid-peripheral), and far peripheral regions were harvested from some animals using a 3 mm trephine. The remaining retinas from these monkeys, and whole retinas from other animals were fixed. RNA isolated from each trephined sample was used for RNase Protection Analysis or real time PCR analysis to quantify opsin mRNA levels from different photoreceptor cell types. Fixed tissue was used for in situ hybridization studies. Human donor eyes (7 glaucoma and 4 control) were obtained from eye banks. All human specimens were used for in situ hybridization studies.


RESULTS
Quantitative mRNA analysis and in situ hybridization studies both showed a reduction in the expression of red/green and blue cone opsin mRNAs in 6 monkey eyes with chronic ocular hypertension, relative to the contralateral eye. No loss of rod opsin mRNA was observed. The principal reduction occurred in cells of the mid-peripheral retina, a region of retina that often shows early and progressive damage in humans with glaucoma. In monkeys with ocular hypertension followed by trabeculectomy, there was a similar decrease in cone opsin mRNAs, but only in six out of fifteen (40%) of the monkeys. The decrease in these animals was correlated with a significantly elevated IOP at some time during the 2 weeks prior to euthanization and not with the extent of glaucomatous damage. Of the 7 human eyes with diagnosed glaucoma that were examined, 5 showed a decrease of cone opsin mRNA in the mid-peripheral retina, whereas none of the 4 normal eyes examined showed a decrease.


CONCLUSIONS
Ocular hypertension leading to glaucoma also affects the outer retina, particularly the cone photoreceptors. We speculate that these cells become stressed leading to a disruption in the expression of normal genes, such as that encoding opsin. There is some evidence that this effect is reversible, when IOP levels are reduced.
Pelzel
Heather R
HR
Department of Ophthalmology and Visual Sciences, University of Wisconsin, Madison, WI 53704, USA.
Schlamp
Cassandra L
CL
Poulsen
Gretchen L
GL
Ver Hoeve
James A
JA
Nork
T Michael
TM
Nickells
Robert W
RW
D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D002102:Cadaver; D005901:Glaucoma / Q000235:genetics* / Q000378:metabolism* / Q000601:surgery; D006801:Humans; D017403:In Situ Hybridization; D008252:Macaca fascicularis; D008253:Macaca mulatta; D008875:Middle Aged; D009798:Ocular Hypertension / Q000235:genetics* / Q000378:metabolism*; D013508:Ophthalmologic Surgical Procedures; D011184:Postoperative Period; D012333:RNA, Messenger / Q000378:metabolism*; D012160:Retina / Q000378:metabolism; D017949:Retinal Cone Photoreceptor Cells / Q000378:metabolism*; D017299:Rod Opsins / Q000235:genetics* / Q000378:metabolism
D012333:RNA, Messenger; D017299:Rod Opsins