Hostname: page-component-cd9895bd7-p9bg8 Total loading time: 0 Render date: 2024-12-24T13:05:35.077Z Has data issue: false hasContentIssue false
  • English
  • Français

Photoreceptors in the rat retina are specifically vulnerable to both hypoxia and hyperoxia

Published online by Cambridge University Press:  06 October 2005

JOHN WELLARD ,
DONALD LEE ,
KRISZTINA VALTER  and
JONATHAN STONE
JOHN WELLARD
Affiliation:
Research School of Biological Sciences, The Australian National University, Canberra, Australia
DONALD LEE
Affiliation:
Department of Anatomy and Histology and Institute for Biomedical Research, The University of Sydney, Australia
KRISZTINA VALTER
Affiliation:
Research School of Biological Sciences, The Australian National University, Canberra, Australia Department of Anatomy and Histology and Institute for Biomedical Research, The University of Sydney, Australia
JONATHAN STONE
Affiliation:
Research School of Biological Sciences, The Australian National University, Canberra, Australia Department of Anatomy and Histology and Institute for Biomedical Research, The University of Sydney, Australia
Get access Rights & Permissions [Opens in a new window]

Abstract

The current study aims to assess the vulnerability of photoreceptors in rat retina to variations in tissue oxygen levels. Young adult Sprague-Dawley rats were exposed to air with the concentration of oxygen set at 10% (hypoxia), 21% (room air, normoxia), and four levels of hyperoxia (45%, 65%, 70%, and 75%), for up to 3 weeks. Their retinas were then examined for cell death, using the TUNEL technique. Hypoxia (10% oxygen) for 2 weeks caused a limited but significant rise in the frequency of TUNEL+ (dying) cells in the retina, the great majority (> 90%) being located in the outer nuclear layer (ONL). Hyperoxia also induced an increase in the frequency of TUNEL+ cells, again predominantly in the ONL. The increase rose with duration of exposure, up to 2 weeks. At 2 weeks exposure, the increase was limited yet significant at 45% oxygen, and maximal at 65%. Where the frequencies of TUNEL+ cells were high, it was evident that photoreceptor death was maximal in the midperipheral retina. The adult retina is vulnerable to maintained shifts in oxygen availability to the retina, both below and above normal. The vulnerability is specific to photoreceptors; other retinal neurons appeared resistant to the exposures tested. Shifts in retinal oxygen levels caused by variations in ambient light, by the persistence of light through the normally dark (night) half of the day–night cycle, or by depletion of the photoreceptor population, may contribute to photoreceptor death in the normal retina.

Keywords

OxygenPhotoreceptor degenerationCritical periodHypoxiaHyperoxia
Type
Research Article
Information
Visual Neuroscience , Volume 22 , Issue 4 , July 2005 , pp. 501 - 507
Copyright
2005 Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

Ahmed, J., Braun, R.D., Dunn, R., & Linsenmeier, R.A. (1993). Oxygen distribution in the macaque retina. Investigative Ophthalmology and Visual Science 34, 516–521.Google Scholar
Ames, A., Li, Y.-Y., Heher, E., & Kimble, C. (1992). Energy metabolism of rabbit retina as related to function: High cost of Na+ transport. Journal of Neuroscience 12, 840–853.Google Scholar
Anderson, B. (1968). Ocular effects of changes in oxygen and carbon dioxide tension. Transactions of the American Ophthalmological Society 66, 423–474.Google Scholar
Anderson, B. & Saltzman, H.A. (1964). Retinal oxygen utilization measured by hyperbaric blackout. Archives of Ophthalmology 72, 792–795.Google Scholar
Arden, G.B. (2001). The absence of diabetic retinopathy in patients with retinitis pigmentosa: Implications for pathophysiology and possible treatment. British Journal of Ophthalmology 85, 366–370.Google Scholar
Bowers, F., Valter, K., Chan, S., Walsh, N., Maslim, J., & Stone, J. (2001). Effects of oxygen and bFGF on the vulnerability of photoreceptors to light damage. Investigative Ophthalmology and Visual Science 42, 804–815.Google Scholar
Butler, F., Harris, D., & Reynolds, R. (1992). Altitude retinopathy on Mount Everest, 1989. Ophthalmology 99, 739–746.Google Scholar
Castorina, C., Campisi, A., Di Giacomo, C., Sorrenti, V., Russo, A., & Vanella, A. (1992). Lipid peroxidation and antioxidant enzymatic systems in rat retina as a function of age. Neurochemical Research 17, 599–604.Google Scholar
Chan-Ling, T. & Stone, J. (1993). Retinopathy of prematurity: Origins in the architecture of the retina. Progress in Retinal and Eye Research 12, 155–176.Google Scholar
Chase, J. (1982). The evolution of retinal vascularization in mammals. A comparison of vascular and avascular retinae. Ophthalmology 89, 1518–1525.Google Scholar
Cringle, S.J. & Yu, D.Y. (2004). Intraretinal oxygenation and oxygen consumption in the rabbit during systemic hyperoxia. Investigative Ophthalmology and Visual Science 45, 3223–3228.Google Scholar
Cringle, S.J., Yu, D.Y., Alder, V., & Su, E.N. (1999). Light and choroidal PO2 modulation of intraretinal oxygen levels in an avascular retina. Investigative Ophthalmology and Visual Science 40, 2307–2313.Google Scholar
Curcio, C.A., Owsley, C., & Jackson, G.R. (2000). Spare the rods, save the cones in aging and age-related maculopathy. Investigative Ophthalmology and Visual Science 41, 2015–2018.Google Scholar
Egensperger, R., Maslim, J., Bisti, S., Hollander, H., & Stone, J. (1996). Fate of DNA from retinal cells dying during development: Uptake by microglia and macroglia (Muller cells). Developmental Brain Research 97, 1–8.Google Scholar
Gao, H. & Hollyfield, J.G. (1992). Aging of the human retina: Differential loss of neurons and retinal pigment epithelium cells. Investigative Ophthalmology and Visual Science 33, 1–17.Google Scholar
Gavrieli, Y., Sherman, Y., & Ben-Sasson, S.A. (1992). Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation. Journal of Cell Biology 119, 493–501.Google Scholar
Jackson, G.R., Owsley, C., Cordle, E.P., & Finley, C.D. (1998). Aging and scotopic sensitivity. Vision Research 38, 3655–3662.Google Scholar
Jackson, G.R., Owsley, C., & Curcio, C.A. (2002). Photoreceptor degeneration and dysfunction in aging and age-related maculopathy. Ageing Research Reviews 1, 381–396.Google Scholar
Lee, A.P., Yamamoto, L.G., & Relles, N.L. (2002). Commercial airline travel decreases oxygen saturation in children. Pediatric Emergency Care 18, 78–80.Google Scholar
Lewis, G., Mervin, K., Valter, K., Maslim, J., Kappel, P.J., Stone, J., & Fisher, S. (1999). Limiting the proliferation and reactivity of retinal Müller cells during experimental retinal detachment: The value of oxygen supplementation. American Journal of Ophthalmology 128, 165–172.Google Scholar
Lewis, G., Talage, K.C., Linberg, K.A., Avery, R.L., & Fisher, S. (2004). The efficacy of delayed oxygen therapy in the treatment of experimental retinal detachment. American Journal of Ophthalmology 137, 1085–1095.Google Scholar
Linsenmeier, R.A. (1986). Effects of light and darkness on oxygen distribution and consumption in the cat retina. Journal of General Physiology 88, 521–542.Google Scholar
Linsenmeier, R.A. & Braun, L.R.D. (1992). Oxygen distribution and consumption in the cat retina during normoxia and hypoxaemia. Journal of General Physiology 99, 177–197.Google Scholar
Linsenmeier, R.A. & Padnick-Silver, L. (2000). Metabolic dependence of photoreceptors on the choroid in the normal and detached retina. Investigative Ophthalmology and Visual Science 41, 3117–3123.Google Scholar
Maslim, J., Valter, K., Egensperger, R., Hollander, H., & Stone, J. (1997). Tissue oxygen during a critical developmental period controls the death and survival of photoreceptors. Investigative Ophthalmology and Visual Science 38, 1667–1677.Google Scholar
McFadden, D., Houston, C., Sutton, J., Powles, A., Gray, G., & Roberts, R. (1981). High-altitude retinopathy. Journal of the American Medical Association 245, 581–586.Google Scholar
McFarland, R.A. & Forbes, W.H. (1940). The effects of variations in the concentration of oxygen and of glucose on dark adaptation. Journal of General Physiology 24, 69–98.Google Scholar
Mervin, K., Valter, K., Maslim, J., Lewis, G., Fisher, S., & Stone, J. (1999). Limiting photoreceptor death and deconstruction during experimental retinal detachment: The value of oxygen supplementation. American Journal of Ophthalmology 128, 155–163.Google Scholar
Mervin, K. & Stone, J. (2002a). Developmental death of photoreceptors in the C57BL/6J mouse: Association with retinal function and self-protection. Experimental Eye Research 75, 703–713.Google Scholar
Mervin, K. & Stone, J. (2002b). Regulation by oxygen of photoreceptor death in the developing and adult C57BL/6J mouse. Experimental Eye Research 75, 715–722.Google Scholar
Nguyen, Q.D., Shah, S.M., Van Anden, E., Sung, J.U., Vitale, S., & Campochiaro, P.A. (2004). Supplemental oxygen improves diabetic macular edema: A pilot study. Investigative Ophthalmology and Visual Science 45, 617–624.Google Scholar
Noell, W.K. (1955). Visual cell effects of high oxygen pressures. Federation Proceedings 14, 107–108.Google Scholar
Penn, J. & Anderson, R. (1991). Effects of light history on the rat retina. Progress in Retinal Research 11, 75–98.Google Scholar
Penn, J.S., Li, S., & Naash, M.I. (2000). Ambient hypoxia reverses retinal vascular attenuation in a transgenic mouse model of autosomal dominant retinitis pigmentosa. Investigative Ophthalmology and Visual Science 41, 4007–4013.Google Scholar
Schedler, O., Kalske, P., & Handschak, H. (2004). Bedside blood gas analysis in airborne rescue operations. Air Medical Journal 23, 36–39.Google Scholar
Schefrin, B.E., Tregear, S.J., Harvey, L.O., & Werner, J.S. (1999). Senescent changes in scotopic contrast sensitivity. Vision Research 39, 3728–3736.Google Scholar
Sternberg, P.M., Landers, M.I.M., & Wolbarsht, M.P. (1984). The negative coincidence of retinitis pigmentosa and proliferative diabetic retinopathy. American Journal of Ophthalmology 97, 788–789.Google Scholar
Stone, J. & Maslim, J. (1997). Mechanisms of retinal angiogenesis. Progress in Retinal and Eye Research 16, 157–181.Google Scholar
Stone, J., Maslim, J., Valter-Kocsi, K., Mervin, K., Bowers, F., Chu, Y., Barnett, N., Provis, J., Lewis, G., Fisher, S.K., Bisti, S., Gargini, C., Cervetto, L., Merin, S., & Peer, J. (1999). Mechanisms of photoreceptor death and survival in mammalian retina. Progress in Retinal and Eye Research 18, 689–735.Google Scholar
Stone, J., Mervin, K., Walsh, N., Valter, K., Provis, J., & Penfold, P. (2004). Photoreceptor stability and degeneration in mammalian retina: Lessons from the edge. In Macular Degeneration: Science and Medicine in Practice, ed. Penfold, P. & Provis, J., pp. 149–165. Heidelberg, Germany: Springer Verlag.
Valter, K., Maslim, J., Bowers, F., & Stone, J. (1998). Photoreceptor dystrophy in the RCS rat: roles of oxygen, debris and bFGF. Investigative Ophthalmology and Visual Science 39, 2427–2442.Google Scholar
Vanderkooi, J.M., Erecinska, M., & Sliver, I.A. (1991). Oxygen in mammalian tissue: Methods of measurement and affinities of various reactions. American Journal of Physiology 260, C1131–1150.Google Scholar
Vingolo, E.M., Pelaia, P., Forte, R., Rocco, M., Giusti, C., & Eduardo, E. (1999). Does hyperbaric oxygen (HBO) delivery rescue retinal photoreceptors in retinitis pigmentosa. Documenta Ophthalmologica 97, 33–39.Google Scholar
Walsh, N., Valter, K., & Stone, J. (2001). Cellular and subcellular patterns of expression of bFGF and CNTF in the normal and light stressed adult rat retina. Experimental Eye Research 72, 495–501.Google Scholar
Walsh, N., van Driel, D., Lee, D., & Stone, J. (2004a). Multiple vulnerability of photoreceptors to mesopic ambient light in the P23H transgenic rat. Brain Research 1013, 194–203.Google Scholar
Walsh, N., Bravo-Nuevo, A., Geller, S., & Stone, J. (2004b). Resistance of photoreceptors in the C57BL/6-C2J, C57BL/6J and BALB/CJ mouse strains to oxygen stress: evidence of an oxygen phenotype. Current Eye Research 29, 441–447.Google Scholar
Wangsa-Wirawan, N.D. & Linsenmeier, R.A. (2003). Retinal oxygen: fundamental and clinical aspects. Archives of Ophthalmology 121, 547–557.Google Scholar
Weleber, R.G. (1994). Retinitis pigmentosa and allied disorders. In Retina, ed. Ryan, S.J., Ogden, T.E., Schachat, A.P., Murphy, R. P. & Glaser, B.M., pp. 335–466. St. Louis, Missouri: Mosby.
Winkler, B.S. (1981). Glycolytic and oxidative metabolism in relation to retinal function. Journal of General Physiology 77, 667–692.Google Scholar
Yamada, H., Yamada, E., Hackett, S.F., Ozaki, H., Okamoto, N., & Campochiaro, P.A. (1999). Hyperoxia causes decreased expression of vascular endothelial growth factor and endothelial cell apoptosis in adult retina. Journal of Cell Physiology 179, 149–156.Google Scholar
Yamada, H., Yamada, E., Ando, A., Esumi, N., Bora, N., Saikia, J., Sung, C.H., Zack, D.J., & Campochiaro, P.A. (2001). Fibroblast growth factor-2 decreases hyperoxia-induced photoreceptor cell death in mice. American Journal of Pathology 159, 1113–1120.Google Scholar
Yu, D.Y. & Cringle, S.J. (2001). Oxygen consumption and distribution within the retina. Progress in Retinal and Eye Research 20, 175–208.Google Scholar
Yu, D.Y., Cringle, S.J., Su, E.N., & Yu, P.K. (2000). Intraretinal oxygen levels before and after photoreceptor loss in the RCS rat. Investigative Ophthalmology and Visual Science 41, 3999–4006.Google Scholar
Yu, D.Y., Cringle, S., Valter, K., Walsh, N., Lee, D., & Stone, J. (2004). Photoreceptor death, trophic factor expression, retinal oxygen status, and photoreceptor function in the P23H rat. Investigative Ophthalmology and Visual Science 45, 2013–2019.Google Scholar