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Electrophysiological consequences of retinal hypoxia

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Abstract

Experiments on cats show that electrical activity of the inner (proximal) retina is unaffected during systemic hypoxia as long as arterial oxygen tension (PaO2) is above 40 mm Hg. This is due to effective regulation of inner retinal tissue PO2 by the retinal circulation. In contrast, some electrical signals generated in the outer (distal) retina begin to change when PaO2 falls below 70–80 mm Hg. The outer retinal responses are generated by the retinal pigment epithelium, but their susceptibility to hypoxia results primarily from their dependence on photoreceptors. Photoreceptor metabolism is sensitive to hypoxia because of the high oxygen consumption of photoreceptors and their reliance on the choroidal circulation, which cannot regulate PO2 in the outer retina. Retinal electrophysiology and oxygen distribution are altered by acutely elevated intraocular pressure just as by hypoxia. These results raise the question as to how inner retinal function can be preserved when outer retinal function is altered. The explanations proposed relate to (1) differences in conditions of light adaptation in different studies, (2) the possible inappropriateness of the previous measurements in the inner retina for revealing photoreceptor dysfunction, and (3) a possible preservation of photoreceptor electrical responses when their metabolism is altered. Comparison of cat and human studies suggests that the human retina is affected in much the same way during hypoxia as the cat retina, but further experiments are required for an understanding of the role of hypoxia in human disease.

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References

  1. Adams CK, Dawson WW, Perez JM, Lieberman HR, Tyler TT (1977) Respiratory stress, visual function and moderation by chemotherapy. Final Report, U.S. Army Research and Development Command, Washington, D.C. (contract DADA17-71-C-1110)

    Google Scholar 

  2. Alder VA, Constable IJ (1981) Effect of hypoxia on the mean firing rate of retinal ganglion cells. Invest Ophthalmol Vis Sci 21:450–456

    PubMed  CAS  Google Scholar 

  3. Alder VA, Cringle SJ (1985) The effect of the retinal circulation on vitreal oxygen tension. Current Eye Res 4:121–129

    Article  CAS  Google Scholar 

  4. Alder VA, Cringle SJ (1988) The effect of raised intraocular pressure on intraretinal oxygen tension profiles (abstr). Invest Ophthalmol Vis Sci [Suppl] 29:247

    Google Scholar 

  5. Alm A, Bill A (1970) Blood flow and oxygen extraction in the cat uvea at normal and high intraocular pressures. Acta Physiol Scand 80:19–28

    PubMed  CAS  Google Scholar 

  6. Alm A, Bill A (1972) The oxygen supply to the retina: I. Effects of changes in intraocular and arterial blood pressures, and in arterial PO2 and PCO2, on the oxygen tension in the vitreous body of the cat. Acta Physiol Scand 84:261–274

    PubMed  CAS  Google Scholar 

  7. Anderson B, Saltzman HA (1964) Retinal oxygen utilization measured by hyperbaric blackout. Arch Ophthalmol 72:792–795

    PubMed  Google Scholar 

  8. Bill A (1984) Circulation in the eye. In: Renkin EM, Michel CC (eds) Handbook of physiology. The cardiovascular system IV. American Physiological Society, Bethesda, Md, pp 1001–1034

    Google Scholar 

  9. Bos GC van den (1968) L’electroretinogramme du chat en cas d’hypoxie. J Physiol (Paris) 60:199–216

    Google Scholar 

  10. Briggs D, Rodenhauser J-H (1973) Distribution and consumption of oxygen in the vitreous body of cats. In: Kessler M, Bruley DF, Clark LC Jr, Lübbers DW, Silver IA, Strauss J (eds) Oxygen supply: theoretical and practical aspects of oxygen supply and microcirculation of tissue. Urban & Scharzenberg, München, pp 265–269

    Google Scholar 

  11. Brown KT, Wiesel TN (1961) Analysis of the intraretinal electroretinogram in the intact cat eye. J Physiol 158:229–256

    PubMed  CAS  Google Scholar 

  12. Brown JL, Hill JA, Burke RE (1957) The effect of hypoxia on the human electroretinogram. Am J Ophthalmol 44:57–67

    PubMed  CAS  Google Scholar 

  13. Carlisle R, Lanphier EH, Rahn H (1964) Hyperbaric oxygen and persistence of vision in retinal ischemia. J Appl Physiol 19:914–918

    PubMed  CAS  Google Scholar 

  14. Dawis S, Hofmann H, Niemeyer GN (1985) The electroretinogram, standing potential and light peak of the perfused cat eye during acid-base changes. Vision Res 25:1163–1177

    Article  PubMed  CAS  Google Scholar 

  15. Drummond JC, Rebuck AS (1981) Effect of hypoxia on the corneoretinal potential in man. Ophthalmic Res 13:213–223

    Google Scholar 

  16. Dyer FN (1988) Effects of low and high oxygen tensions and related respiratory conditions in visual performance: a literature review. US Army Aeromedical Research Laboratory Report 88-7. Defense Technical Information Center, Alexandria, Virginia

    Google Scholar 

  17. Enroth-Cugell C, Goldstick TK, Linsenmeier RA (1980) The contrast sensitivity of cat retinal ganglion cells at reduced oxygen tensions. J Physiol (Lond) 304:59–81

    CAS  Google Scholar 

  18. Ernest JT, Goldstick TK (1983) Response of choroidal vascular resistance to hyperglycemia. Int Ophthalmol 6:119–124

    Article  PubMed  CAS  Google Scholar 

  19. Fenn WO, Galambos R, Otis AB, Rahn H (1949) Corneoretinal potential in anoxia and acapnia. J Appl Physiol 1:710–716

    PubMed  CAS  Google Scholar 

  20. Frisancho AR (1975) Functional adaptation to high altitude hypoxia. Science 187:313–319

    Article  PubMed  CAS  Google Scholar 

  21. Fujino T, Hamasaki D (1967) Effect of intraocular pressure on the electroretinogram. Arch Ophthalmol 78:755–765

    Google Scholar 

  22. Granit R (1933) The components of the retinal action potential and their relation to the discharge in the optic nerve. J Physiol 77:207–240

    PubMed  CAS  Google Scholar 

  23. Grehn F, Grüser O-J, Stange D (1984) Effect of short-term intraocular pressure increase on cat retinal ganglion cell activity. Behav Brain Res 14:109–121

    Article  PubMed  CAS  Google Scholar 

  24. Griff ER, Steinberg RH (1984) Changes in apical [K+]0 produce delayed basal membrane responses of the retinal pigment epithelium in the gecko. J Gen Physiol 83:191–211

    Article  Google Scholar 

  25. Guyton AC (1976) Aviation, high altitude and space physiology. In: Textbook of medical physiology. 5th edn. Saunders, Philadelphia, pp 586–597

    Google Scholar 

  26. Halstead WC (1945) Chronic intermittent anoxia and impairment of peripheral vision. Science 101:615–616

    Article  PubMed  Google Scholar 

  27. Haugh LM, Linsenmeier RA, Goldstick TK (1989) Mathematical models of the spatial distribution of retinal oxygen tension and consumption, including changes upon illumination. Ann Biomed Eng (in press)

  28. Hecht S, Hendley CD, Frank SR, Haig C (1946) Anoxia and brightness discrimination. J Gen Physiol 29:335–351

    Article  CAS  Google Scholar 

  29. Hochachka PW (1986) Defense strategies against hypoxia and hypothermia. Science 231:234–241

    Article  PubMed  CAS  Google Scholar 

  30. Hood DC, Greenstein V (1989) Inferring the site of disease action from rod incremental threshold (TVI) data. Vision Res (in press)

  31. Kobrick JL, Appleton B (1971) Effects of extended hypoxia on visual performance and retinal vascular state. J Appl Physiol 31:357–362

    PubMed  CAS  Google Scholar 

  32. Kolder H (1959) Spontane and experimentelle Änderungen des Bestandpotentials des menschlichen Auges. Pflügers Arch 268:258–272

    Article  PubMed  CAS  Google Scholar 

  33. Linsenmeier RA (1986) Effects of light and darkness on oxygen distribution and consumption in the cat retina. J Gen Physiol 88:521–542

    Article  PubMed  CAS  Google Scholar 

  34. Linsenmeier RA, Steinberg RH (1982) Origin and sensitivity of the light peak of the intact cat eye. J Physiol (Lond) 331:653–673

    CAS  Google Scholar 

  35. Linsenmeier RA, Steinberg RH (1984) Delayed basal hyperpolarization of cat retinal pigment epithelium, and its relation to the fast oscillation of the DC electroretinogram. J Gen Physiol 83:213–232

    Article  PubMed  CAS  Google Scholar 

  36. Linsenmeier RA, Steinberg RH (1984) Effects of hypoxia on potassium homeostasis and pigment epithelial cells in the cat retina. J Gen Physiol 84:945–970

    Article  PubMed  CAS  Google Scholar 

  37. Linsenmeier RA, Steinberg RH (1986) Mechanisms of hypoxic effects on the cat DC electroretinogram. Invest Ophthalmol Vis Sci 27:1385–1394

    PubMed  CAS  Google Scholar 

  38. Linsenmeier RA, Yancey CM (1987) Improved fabrication of double-barreled recessed cathode oxygen microelectrodes. J Appl Physiol 63:2554–2557

    PubMed  CAS  Google Scholar 

  39. Linsenmeier RA, Mines AH, Steinberg RH (1983) Effects of hypoxia and hypercapnia on the light peak and electroretinogram of the cat. Invest Ophthalmol Vis Sci 24:37–46

    PubMed  CAS  Google Scholar 

  40. Linsenmeier RA, Smith VC, Pokorny J (1987) The light rise of the electrooculogram during hypoxia. Clin Vis Sci 2:111–116

    Google Scholar 

  41. Marmor MF, Donovan WJ, Gaba DM (1985) Effects of hypoxia and hyperoxia on the human standing potential. Doc Ophthalmol 60:347–352

    Article  PubMed  CAS  Google Scholar 

  42. Masland RH, Ames A III (1975) Dissociation of field potential from neuronal activity in the isolated retina: failure of the b-wave with normal ganglion level response. J Neurobiol 6:305–312

    Article  PubMed  CAS  Google Scholar 

  43. McFarland RA, Evans JN (1939) Alterations in dark adaptation under reduced oxygen tensions. Am J Physiol 127:37–50

    CAS  Google Scholar 

  44. Messner G, Wang W, Paulmichl M, Oberleithner H, Lang F (1985) Ouabain decreases apparent potassium conductance in proximal tubules of the amphibian kidney. Pflügers Arch 404:131–137

    Article  PubMed  CAS  Google Scholar 

  45. Niemeyer G, Nagahara K, Demant E (1982) Effects of changes in arterial PO2 and PCO2 on the ERG in the cat. Invest Ophthalmol Vis Sci 23:678–683

    PubMed  CAS  Google Scholar 

  46. Noell WK (1951) Site of asphyxial block in mammalian retinae. J Appl Physiol 3:489–500

    PubMed  CAS  Google Scholar 

  47. Oakley B II (1977) Potassium and the photoreceptor dependent pigment epithelial hyperpolarization. J Gen Physiol 70:405–424

    Article  PubMed  CAS  Google Scholar 

  48. Oakley B II, Green DG (1976) Correlation of light-induced changes in retinal extracellular potassium concentration with c-wave of the electroretinogram. J Neurophysiol 39:1117–1133

    PubMed  CAS  Google Scholar 

  49. Oakley B II, Flaming DG, Brown KT (1979) Effects of the rod receptor potential upon extracellular potassium ion concentration. J Gen Physiol 74:713–737

    Article  PubMed  CAS  Google Scholar 

  50. Orr HT, Lowry OH, Cohen AI, Ferrendelli JA (1976) Distribution of 3′:5′-cyclic AMP and 3′:5′-cyclic GMP in rabbit retina in vivo: selective effects of dark and light adaptation and ischemia. Proc Natl Acad Sci USA 73:4442–4445

    Article  PubMed  CAS  Google Scholar 

  51. Palmer LG, Sakin H (1988) Regulation of renal ion channels. FASEB J 2:3061–3065

    PubMed  CAS  Google Scholar 

  52. Rodieck RW (1972) Components of the electroretinogram — a reappraisal. Vision Res 12:773–780

    Article  PubMed  CAS  Google Scholar 

  53. Sickel W (1972) Retinal metabolism in dark and light: physiology of photoreceptor organs. In: Fuortes MGF (ed) Handbook of sensory physiology, vol 2. Springer, Berlin Heidelberg New York, pp 667–727

    Google Scholar 

  54. Skoog K-O (1975) The directly recorded standing potential of the human eye. Acta Ophthalmol 53:120–132

    Article  CAS  Google Scholar 

  55. Stefansson E, Wolbarsht ML, Landers MB III (1983) In vivo O2 consumption in rhesus monkeys in light and dark. Exp Eye Res 37:251–256

    Article  PubMed  CAS  Google Scholar 

  56. Steinberg RH (1969) Comparison of the intraretinal b-wave and d.c. component in the area centralis of cat retina. Vision Res 9:317–331

    Article  PubMed  CAS  Google Scholar 

  57. Steinberg RH (1987) Monitoring communications between photoreceptors and pigment epithelial cells: effects of “mild” systemic hypoxia. Invest Ophthalmol Vis Sci 28:1888–1904

    PubMed  CAS  Google Scholar 

  58. Steinberg RH, Linsenmeier RA, Griff ER (1985) Retinal pigment epithelial cell contributions to the electroretinogram and electrooculogram. Prog Retinal Res 4:33–66

    Article  Google Scholar 

  59. Täumer T, Hennig J, Wolff L (1976) Further investigations concerning the fast oscillation of the retinal potential. Bibl Ophthalmol 85:57–67

    PubMed  Google Scholar 

  60. Tsacopoulos M (1979) Le rôle des facteurs métaboliques dans la régulation du débit sanguin rétinien. Adv Ophthalmol 39:233–273

    PubMed  CAS  Google Scholar 

  61. Winkler BS (1975) Dependence of rat and rabbit photoreceptor potentials upon anaerobic and aerobic metabolism in vitro. Exp Eye Res 21:545–548

    Article  PubMed  CAS  Google Scholar 

  62. Yancey CM, Linsenmeier RA (1988) The electroretinogram and choroidal PO2 in the cat during elevated intraocular pressure. Invest Ophthalmol Vis Sci 29:700–707

    PubMed  CAS  Google Scholar 

  63. Yancey CM, Linsenmeier RA (1989) Oxygen distribution and consumption in the cat retina at increased intraocular pressure. Invest Ophthalmol Vis Sci 30:600–611

    PubMed  CAS  Google Scholar 

  64. Zuckerman R, Weiter JJ (1980) Oxygen transport in the bullfrog retina. Exp Eye Res 30:117–127

    Article  PubMed  CAS  Google Scholar 

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Linsenmeier, R.A. Electrophysiological consequences of retinal hypoxia. Graefe’s Arch Clin Exp Ophthalmol 228, 143–150 (1990). https://doi.org/10.1007/BF02764309

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