Hostname: page-component-78c5997874-ndw9j Total loading time: 0 Render date: 2024-11-03T09:17:21.870Z Has data issue: false hasContentIssue false
  • English
  • Français

Long-term ERG analysis in the partially light-damaged mouse retina reveals regressive and compensatory changes

Published online by Cambridge University Press:  09 March 2006

ADAM RICHARDS ,
ALFRED A. EMONDI  and
BAERBEL ROHRER
ADAM RICHARDS
Affiliation:
Department of Neurosciences, Medical University of South Carolina, Charleston, South Carolina
ALFRED A. EMONDI
Affiliation:
Institute for Sensory Research, Syracuse University, Syracuse, New York Space and Naval Warfare Systems Center, Charleston, South Carolina
BAERBEL ROHRER
Affiliation:
Department of Neurosciences, Medical University of South Carolina, Charleston, South Carolina Department of Ophthalmology, Medical University of South Carolina, Charleston, South Carolina
Get access Rights & Permissions [Opens in a new window]

Abstract

Most of the blinding retinopathies are due to progressive photoreceptor degeneration. Treatment paradigms that are currently being investigated include strategies to either halt or slow down photoreceptor cell loss, or to replace useful vision with retinal prosthesis. However, more information is required on the pathophysiological changes of the diseased retina, in particular the inner retina, that occur as a consequence of photoreceptor cell loss. Here we wished to use light damage as a stoppable insult to determine the structural and functional consequences on inner and outer retina, with the overall goal of determining whether survival of a functional inner retina is possible even if the outer retina is damaged. Mice were exposed to a 20-day light-damage period. Electroretinograms (ERG) and morphology were used to assess subsequent recovery. Outer retina was monitored analyzing a-waves, which represent photoreceptor cell responses, and histology. Integrity of the inner retina was monitored, analyzing b-waves and oscillatory potentials (OP1–OP4) and immunohistochemical markers for known proteins of the inner retina. All six ERG components were significantly suppressed with respect to amplitudes and kinetics, but stabilized in a wave-dependent manner within 40–70 days after the end of light exposure. As expected, damage of the outer retina was permanent. However, function of the inner retina was found to recover significantly. While b-wave amplitudes remained suppressed to 60% of their baseline values, OP amplitudes recovered completely, and implicit times of all components of the inner retina (b-wave and OP1–OP4) recovered to a level close to baseline values. Histological analyses confirmed the lack of permanent damage to the inner retina. In summary, these data suggests that the inner retina has the potential for significant recovery as well as plasticity if treatment is available to stop the deterioration of the outer retina.

Keywords

ElectroretinogramOscillatory potentialsSynaptic compensation
Type
Research Article
Information
Visual Neuroscience , Volume 23 , Issue 1 , January 2006 , pp. 91 - 97
Copyright
2006 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

Aleman, T.S., LaVail, M.M., Montemayor, R., Ying, G., Maguire, M.M., Laties, A.M., Jacobson, S.G., & Cideciyan, A.V. (2001). Augmented rod bipolar cell function in partial receptor loss: An ERG study in P23H rhodopsin transgenic and aging normal rats. Vision Research 41, 2779–2797.Google Scholar
Bayer, A.U., Cook, P., Brodie, S.E., Maag, K.P., & Mittag, T. (2001). Evaluation of different recording parameters to establish a standard for flash electroretinography in rodents. Vision Research 41, 2173–2185.Google Scholar
Cortina, M.S., Gordon, W.C., Lukiw, W.J., & Bazan, N.G. (2003). Light-induced photoreceptor damage triggers DNA repair: differential fate of rods and cones. Advances in Experimental Medicine and Biology 533, 229–240.Google Scholar
Danciger, M., Matthes, M.T., Yasamura, D., Akhmedov, N.B., Rickabaugh, T., Gentleman, S., Redmond, T.M., LaVail, M.M., & Farber, D.B. (2000). A QTL on distal chromosome 3 that influences the severity of light-induced damage to mouse photoreceptors. Mammalian Genome. 11, 422–427.Google Scholar
Delyfer, M.N., Leveillard, T., Mohand-Said, S., Hicks, D., Picaud, S., & Sahel, J.A. (2004). Inherited retinal degenerations: Therapeutic prospects. Biology of the Cell 96, 261–269.Google Scholar
Faktorovich, E.G., Steinberg, R.H., Yasamura, D., Matthes, M.T., & LaVail, M.M. (1992). Basic fibroblast growth factor and local injury protect photoreceptors from light damage in the rat. Journal of Neuroscience 12, 3554–3567.Google Scholar
Gresh, J., Goletz, P.W., Crouch, R.K., & Rohrer, B. (2003). Structure–function analysis of rods and cones in juvenile, adult, and aged C57bl/6 and Balb/c mice. Visual Neuroscience 20, 211–220.Google Scholar
Grunert, U., Martin, P.R., & Wassle, H. (1994). Immunocytochemical analysis of bipolar cells in the macaque monkey retina. Journal of Comparative Neurology 348, 607–627.Google Scholar
Haverkamp, S. & Wassle, H. (2000). Immunocytochemical analysis of the mouse retina. Journal of Comparative Neurology 424, 1–23.Google Scholar
Hetling, J.R. & Baig-Silva, M.S. (2004). Neural prostheses for vision: Designing a functional interface with retinal neurons. Neurological Research 26, 21–34.Google Scholar
LaVail, M.M., Gorrin, G.M., & Repaci, M.A. (1987). Strain differences in sensitivity to light-induced photoreceptor degeneration albino mice. Current Eye Research 6, 825–834.Google Scholar
Li, Z.Y., Tso, M.O., Wang, H.M., & Organisciak, D.T. (1985). Amelioration of photic injury in rat retina by ascorbic acid: A histopathologic study. Investigative Ophthalmology and Visual Science 26, 1589–1598.Google Scholar
Lyubarsky, A.L., Falsini, B., Pennesi, M.E., Valentini, P., & Pugh, E.N., Jr. (1999). UV- and midwave-sensitive cone-driven retinal responses of the mouse: A possible phenotype for coexpression of cone photopigments. Journal of Neuroscience 19, 442–455.Google Scholar
Lyubarsky, A.L. & Pugh, E.N., Jr. (1996). Recovery phase of the murine rod photoresponse reconstructed from electroretinographic recordings. Journal of Neuroscience 16, 563–571.Google Scholar
Machida, S., Kondo, M., Jamison, J.A., Khan, N.W., Kononen, L.T., Sugawara, T., Bush, R.A., & Sieving, P.A. (2000). P23H rhodopsin transgenic rat: Correlation of retinal function with histopathology. Investigative Ophthalmology and Visual Science 41, 3200–3209.Google Scholar
Marc, R.E., Jones, B.W., Watt, C.B., & Strettoi, E. (2003). Neural remodeling in retinal degeneration. Progress in Retinal Eye Research 22, 607–655.Google Scholar
Marrone, D.F., LeBoutillier, J.C., & Petit, T.L. (2004). Changes in synaptic ultrastructure during reactive synaptogenesis in the rat dentate gyrus. Brain Research 1005, 124–136.Google Scholar
McIntire, W.E., Dingus, J., Schey, K.L., & Hildebrandt, J.D. (1998). Characterization of the major bovine brain Go alpha isoforms. Mapping the structural differences between the alpha subunit isoforms identifies a variable region of the protein involved in receptor interactions. Journal of Biological Chemistry 273, 33135–33141.Google Scholar
Noell, W.K., Organisciak, D.T., Ando, H., Braniecki, M.A., & Durlin, C. (1987). Ascorbate and dietary protective mechanisms in retinal light damage of rats: Electrophysiological, histological and DNA measurements. Progress in Clinical Biological Research 247, 469–483.Google Scholar
Ohira, A., Tanito, M., Kaidzu, S., & Kondo, T. (2003). Glutathione peroxidase induced in rat retinas to counteract photic injury. Investigative Ophthalmology and Visual Science 44, 1230–1236.Google Scholar
Penn, J.S. & Anderson, R.E. (1992). Effects of light history on the rat retina. In Progress in Retinal Research, Vol. 11, ed. Osborne, N. & Chader, G., pp. 75–98. New York: Pergamon Press.
Penn, J.S. & William, T.P. (1986). Photostasis: Regulation of daily photon-catch by rat retinas in response to various cyclic illuminances. Experimental Eye Research 43, 915–928.Google Scholar
Rice, D.S. & Curran, T. (2000). Disabled-1 is expressed in type AII amacrine cells in the mouse retina. Journal of Comparative Neurology 424, 327–338.Google Scholar
Rohrer, B. (2001). Gene dosage effect of the TrkB receptor on rod physiology and biochemistry in juvenile mouse retina. Molecular Vision 7, 288–296.Google Scholar
Rohrer, B., Korenbrot, J.I., LaVail, M.M., Reichardt, L.F., & Xu, B. (1999). Role of neurotrophin receptor TrkB in the maturation of rod photoreceptors and establishment of synaptic transmission to the inner retina. Journal of Neuroscience 19, 8919–8930.Google Scholar
Rohrer, B., Matthes, M.T., LaVail, M.M., & Reichardt, L.F. (2003). Lack of p75 receptor does not protect photoreceptors from light-induced cell death. Experimental Eye Research 76, 125–129.Google Scholar
Singer, W. (1990). The formation of cooperative cell assemblies in the visual cortex. Journal of Experimental Biology 153, 177–197.Google Scholar
Tanito, M., Masutani, H., Nakamura, H., Ohira, A., & Yodoi, J. (2002). Cytoprotective effect of thioredoxin against retinal photic injury in mice. Investigative Ophthalmology and Visual Science 43, 1162–1167.Google Scholar
Vardi, N. (1998). Alpha subunit of Go localizes in the dendritic tips of ON bipolar cells. Journal of Comparative Neurology 395, 43–52.Google Scholar