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Expression of a mutant opsin gene increases the susceptibility of the retina to light damage

Published online by Cambridge University Press:  02 June 2009

Min Wang ,
Tim T. Lam ,
Mark O.M. Tso  and
Muna I. Naash
Min Wang
Affiliation:
Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, IL
Tim T. Lam
Affiliation:
Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, IL
Mark O.M. Tso
Affiliation:
Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, IL
Muna I. Naash
Affiliation:
Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, IL
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Abstract

The question of whether the expression of mutant opsin predisposes the retina to light damage was addressed using transgenic mice that express rhodopsin with three point mutations near the N-terminus of the molecule. The mutations involve the substitution of histidine for proline at position 23 (P23H), glycine for valine at position 20 (V20G), and leucine for proline at position 27 (P27L). These mice express equal amounts of mutant and wild-type transcripts, and develop a progressive photoreceptor degeneration that is similar to that seen in human retinitis pigmentosa (RP). The P23H mutation is associated with the most frequently occurring form of human autosomal dominant retinitis pigmentosa (ADRP) in the United States. Transgenic and normal littermates were exposed to illuminance of 300 foot-candles (ft-c) for 24 h, then placed in darkness for either 6 h, 6 days, or 14 days. Histological and biochemical techniques were used to evaluate the outer retina in light-exposed and control animals reared on 12-h light/12-h dark cycle. The results indicate that light exposure accelerates the pathological changes associated with the transgene expression. Compared with transgenic animals reared in ambient cyclic light, retinas from light-exposed mice had a reduced rhodopsin content, fewer photoreceptor cell bodies, and less preservation of retinal structure. Data obtained from normal mice did not differ for the lighting regimens used. These findings suggest that the expression of VPP mutations in the opsin gene predisposes the transgenic photoreceptors to be more susceptible to light damage. The data also suggest that reducing photic exposure may be beneficial to any patient with RP mediated by an opsin mutation.

Keywords

Autosomal dominant retinitis pigmentosaAnimal modelLight damageMutant opsinTransgenic mice
Type
Research Articles
Information
Visual Neuroscience , Volume 14 , Issue 1 , January 1997 , pp. 55 - 62
Copyright
Copyright © Cambridge University Press 1997

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References

Al-Ubaidi, M.R., Pittler, S.J., Champagne, M.S., Triantafyllos, J.T., McGinnis, J.F. & Baehr, W. (1990). Mouse opsin. Gene structure and molecular basis of multiple transcripts. Journal of Biological Chemistry 265, 20563–20569.CrossRefGoogle ScholarPubMed
Baehr, W., Falk, I.D., Bugra, K., Triantafyllos, J.T. & McGinnis, J.F. (1988). Isolation and molecular analysis of the mouse opsin gene. FEBS Letters 238, 253–256.CrossRefGoogle ScholarPubMed
Berson, E.L. (1971). Light deprivation for early retinitis pigmentosa: A hypothesis. Archives of Ophthalmology 85, 521–529.CrossRefGoogle ScholarPubMed
Berson, E.L. (1980). Light deprivation and retinitis pigmentosa. Vision Research 20, 1179–1184.CrossRefGoogle ScholarPubMed
Berson, E.L., Rosner, B., Sandberg, M.A. & Dryja, T.P. (1991). Ocular findings in patients with autosomal dominant retinitis pigmentosa and a rhodopsin gene defect (Pro-23-His). Archives of Ophthalmology 109, 92–101.CrossRefGoogle Scholar
Berson, E.L. (1993). Retinitis pigmentosa. Investigative Ophthalmology and Visual Science 34, 1659–1676.Google ScholarPubMed
Birch, D.G., Hood, D.C., Nusinowitz, S. & Pepperberg, D.R. (1995). Abnormal activation and inactivation mechanisms of rod transducin in patients with autosomal dominant retinitis pigmentosa and the Pro-23-His mutation. Investigative Ophthalmology and Visual Science 36, 1603–1614.Google ScholarPubMed
Cheng, T. & Naash, M.I. (1995). Quantitative analysis of mRNA levels of the transgenic and endogenous opsin genes in retinas of transgenic mice. Investigative Ophthalmology and Visual Science 36, S273.Google Scholar
Critchett, A. (1919). A biotrophy of the retinal neuroepithelium or ‘retinitis pigmentosa.’ Transactions of the Ophthalmological Society (U.K.) 49, 165–195.Google Scholar
Dryja, T.P., Hahn, L.B., Cowley, G.S., McGee, T.L. & Berson, E.L. (1991). Mutation spectrum of the rhodopsin gene among patients with autosomal dominant retinitis pigmentosa. Proceedings of the National Academy of Sciences of the U.S.A. 88, 9370–9374.CrossRefGoogle ScholarPubMed
Ginsberg, H.M. & LaVail, M.M. (1985). Light-induced retinal degeneration in the mouse: Analysis of pigmentation mutants. In Retinal Degeneration: Experimental and Clinical Studies, ed. LaVail, M.M., Hollyfield, J.G. & Anderson, R.E., pp. 449–469. New York: Alan R. Liss, Inc.Google Scholar
Goto, Y., Peachey, N.S., Ripps, H. & Naash, M.I. (1995). Functional abnormalities in transgenic mice expressing a mutant rhodopsin gene. Investigative Ophthalmology and Visual Science 36, 62–71.Google ScholarPubMed
Goto, Y., Peachey, N.S., Ziroli, N.S., Seiple, W.H., Gryczan, C., Pepperberg, D.R. & Naash, M.I. (1996). Rod phototransduction in transgenic mice expressing a mutant opsin gene. Journal Optical Society of America A 13, 577–585.Google ScholarPubMed
Gryczan, C., Kuszak, J.R., Novak, L., Peachey, N.S., Goto, Y. & Naash, M.I. (1995). A transgenic mouse model for autosomal dominant retinitis pigmentosa caused by a three base pair deletion in codon 255/256 of the opsin gene. Investigative Ophthalmology and Visual Science (Abstract) 36, S423.Google Scholar
Heckenlively, J.R., Rodriguez, J.A. & Daiger, S.P. (1991). Autosomal dominant sectoral retinitis pigmentosa. Archives of Ophthalmology 109, 84–91.CrossRefGoogle ScholarPubMed
Kemp, C.M., Jacobson, S.G., Roman, A.J., Sung, C. & Nathans, J. (1992). Abnormal rod dark adaptation in autosomal dominant retinitis pigmentosa with proline-23-histidine rhodopsin mutation. American Journal of Ophthalmology 113, 165–174.CrossRefGoogle ScholarPubMed
Lamb, T.D. (1990). Dark adaptation: A re-examination. In Night Vision, ed. Hess, R.F. & Nordby, L.T., pp. 177–222. Cambridge, Massachusetts: Cambridge University Press.Google Scholar
LaVail, M.M., Gorrin, G.M., Ginsberg, H.M., Thomas, L. & Henderson, M. (1986). Evidence for genetic regulation of light damage. Investigative Ophthalmology and Visual Science 27, 55Google Scholar
LaVail, M.M., Gorrin, G.M. & Repaci, M.A. (1987). Strain differences in sensitivity to light-induced photoreceptor degeneration in albino mice. Current Eye Research 6, 825–834.CrossRefGoogle ScholarPubMed
LaVail, M.M., White, M.P., Gorrin, G.M., Yasumura, D., Porrello, K.V. & Mullen, R.J. (1993). Retinal degeneration in the nervous mutant mouse. I. Light microscopic cytopathology and changes in the interphotoreceptor matrix. Journal of Comparative Neurology 333, 168–181.CrossRefGoogle ScholarPubMed
Leber, T. (1916). Die pigmentdegeneration der netzhaut und mit ihr verwandte erkrankungen. In Handbuch der Gesamten Augenheilkunde, ed. Saemisch-Hess, G., vol. 7, pp. 1076–1225. Leipzig, West Germany: Engelmann.Google Scholar
Li, T., Franson, W.K., Gordon, J.W., Berson, E.L. & Dryja, T.P. (1995). Constitutive activation of phototransduction by K296E opsin is not a cause of photoreceptor degeneration. Proceedings of the National Academy of Sciences of the U.S.A. 92, 3551–3555.CrossRefGoogle Scholar
Li, Z., Jacobson, S.O. & Milam, A.H. (1994). Autosomal dominant retinitis pigmentosa caused by the threonine-17-methionine rhodopsin mutation: Retinal histopathology and immunocytochemistry. Experimental Eye Research 58, 397–408.CrossRefGoogle ScholarPubMed
Miyake, Y., Sugita, S., Horiguchi, M. & Yagasaki, K. (1990). Light deprivation and retinitis pigmentosa. American Journal of Ophthalmology 110, 305–306.CrossRefGoogle ScholarPubMed
Naash, M.I., LaVail, M.M. & Anderson, R.E. (1989). Factors affecting the susceptibility of the retina to light damage. In Inherited and Environmentally Induced Retinal Degenerations, ed. LaVail, M.M., Anderson, R.E. & Hollyfield, J.G., pp. 513–522. New York: Alan R. Liss.Google Scholar
Naash, M.I., Al-Ubaidi, M.R., Hollyfield, J.G. & Baehr, W. (1993 a). Simulation of autosomal dominant retinitis pigmentosa in transgenic mice. In Retinal Degeneration, ed. Hollyfield, J.G., Anderson, R.E. & LaVail, M.M., pp. 202–210. New York: Plenum Press.Google Scholar
Naash, M.I., Hollyfield, J.G., Al-Ubaidi, M.R. & Baehr, W. (1993 b). Simulation of human autosomal dominant retinitis pigmentosa in transgenic mice expressing a mutated murine opsin gene. Proceedings of the National Academy of Sciences of the U.S.A. 90, 5499–5503.CrossRefGoogle ScholarPubMed
Naash, M.I., Peachey, N.S., Li, Z., Gryczan, C.C., Goto, Y., Blanks, J., MIlam, A.H. & Ripps, H. (1996). Light-induced acceleration of photoreceptor degeneration in transgenic mice expressing mutant opsin. Investigative Ophthalmology and Visual Science 37, 775–782.Google Scholar
Noell, W.K., Walker, V.S., Kang, B.S. & Berman, S. (1966). Retinal damage by light in rats. Investigative Ophthalmology and Visual Science 5, 450–473.Google ScholarPubMed
Olsson, J.E., Gordon, J.W., Pawlyk, B.S., Roof, D., Hayes, A., Molday, R.S., Mukai, S., Cowley, G.S., Berson, E.L. & Dryja, T.P. (1992). Transgenic mice with a rhodopsin mutation (Pro23His): A mouse model of autosomal retinitis pigmentosa. Neuron 9, 815–830.CrossRefGoogle Scholar
Organisciak, D.T. & Winkler, B.S. (1994). Retinal light damage: Practical and theoretical considerations. Progress in Retina Eye Research 13, 1–29.CrossRefGoogle Scholar
Rapp, L.M., Naash, M.I., Wiegand, R.D., Joel, C.D., Nielsen, J.C. & Anderson, R.E. (1985). Morphological and biochemical comparisons between retinal regions having differing susceptibility to photoreceptor degeneration. In Retinal Degeneration: Experimental and Clinical Studies, ed. LaVail, M.M., Hollyfield, J.G. & Anderson, R.E., pp. 421–437. New York: Alan R. Liss, Inc.Google Scholar
Sandberg, M., Weigel-DiFranco, C., Dryja, T. & Berson, E. (1996). Clinical expression correlates with location of rhodopsin mutation in dominant retinitis pigmentosa. Investigative Ophthalmology and Visual Science 36, 1934–1942.Google Scholar
Sanyal, S. & Hawkins, R.K. (1986). Development and degeneration of retina in rds mutant mice: Effects of light on the rate of degeneration in albino and pigmented homozygous and heterozygous mutant and normal mice. Vision Research 26, 1177–1185.CrossRefGoogle ScholarPubMed
Smith, S.B., Cope, B.K. & McCoy, J.R. (1994). Effects of dark-rearing on the retinal degeneration of the C57BL/6-mivit/mivit mouse. Experimental Eye Research 58, 77–84.CrossRefGoogle ScholarPubMed
Smith, W.C., Adamus, G., Van Der Wel, H., Timmers, A., Palczewski, K., Ulshafer, R.J., Harhrave, P.A. & McDowell, J.H. (1995). Alligator rhodopsin: Sequence and biochemical properties. Experimental Eye Research 61, 569–578.CrossRefGoogle ScholarPubMed
Stone, E.S., Kimura, A.E., Nichols, B.E., Khadivi, P., Fishman, G.A. & Sheffield, V.C. (1991). Regional distribution of retinal degeneration in patients with the proline to histidine mutation in codon 23 of the rhodopsin gene. Ophthalmology 98, 1806–1813.CrossRefGoogle ScholarPubMed
Stryer, L. (1988). Molecular basis of visual excitation. Cold Spring Harbor Symposium on Quantitative Biology 53, 283–294.CrossRefGoogle ScholarPubMed
Sung, C., Schneider, B.G., Agarwal, N., Papermaster, D.S. & Nathans, J. (1991). Functional heterogeneity of mutant rhodopsins responsible for autosomal dominant retinitis pigmentosa. Proceedings of the National Academy of Sciences of the U.S.A. 88, 8840–8844.CrossRefGoogle ScholarPubMed
Ting, T.D., Wu, T.-H., Okajima, T.-I.L., Pepperberg, D.R. & Naash, M.I. (1995). Analysis of rhodopsin and retinoids in a transgenic mouse model of ADRP. Investigative Ophthalmology and Visual Science (Abstract) 36, S5.Google Scholar
Williams, T.P., Howell, W.L. (1983) Action spectrum of retinal light damage in albino rats. Investigative Ophthalmology and Visual Science 24, 285–287.Google ScholarPubMed
Wu, T.-H., Li, S., Kogut, N.S., Peachey, N. & Naash, M.I. (1996). Expression of P23H mutation in transgenic mice as a model for one form of human autosomal dominant retinitis pigmentosa. Investigative Ophthalmology and Visual Science (Abstract) 37, S999.Google Scholar
Zhang, M., Quiambao, A., Lam, T., Zhang, S. & Tso, M. (1994). The effect of light exposure on photoreceptor degeneration in transgenic mice with SV40T antigen. Investigative Ophthalmology and Visual Science (Abstract) 93, 1517.Google Scholar