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Hyperoxia, hyperglycemia, and photoreceptor sensitivity in normal and diabetic subjects



The aim of this study was to investigate the effects of an increase in the saturation of blood oxygen (SaO2) and/or serum glucose on photoreceptor sensitivity in normal subjects and in patients with diabetes mellitus. We monitored cone and rod sensitivity by recording dark-adaptation curves to both green and red test stimuli while inhaling either air (20% O2 + 80% N2) or 100% oxygen in 12 normal subjects and 12 diabetic patients with no (10) or mild (2) retinopathy. We also repeated the experiment in 10 of the normal subjects under hyperglycemia (mean serum glucose: 161 mg/dl). Results show that in normal subjects the dark-adapted cone sensitivity is improved by an increase in SaO2 or by hyperglycemia. Final rod sensitivity is unchanged during hyperoxia and during hyperglycemia when measured with a green test spot. However the kinetics of dark adaptation are altered during hyperglycemia, and an increase in final sensitivity is observed when measured with the red test spot. Inhalation of oxygen during hyperglycemia in normal subjects reduces cone sensitivity compared to that found during hyperglycemia alone (Pasteur effect). In diabetic subjects the dark-adapted cone threshold is comparable to that found in normal subjects, and sensitivity also increases with an increase in SaO2. The final rod threshold, however, is impaired compared to that of the control group, and rod sensitivity is improved by increasing the SaO2. The results suggest that the metabolism of rods and cones may differ in normal subjects: in cones, the rate of metabolism can be augmented by increasing the available oxygen or glucose, whereas rods appear more insensitive to increased blood oxygen saturation and hyperglycemia. In diabetic subjects, both cone and rod metabolism can be increased by supplemental oxygen, indicative of an early rod deficit. The study lends weight to the hypothesis that dark-adapted rods in diabetics are hypoxic before the onset of retinopathy.


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Address correspondence and reprint requests to: Anne Kurtenbach, University Eye Hospital, Schleichstrasse 12-16, 72076 Tuebingen, Germany. E-mail:


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Ahmed, J., Braun, R.D., Dunn, R., Jr., & Linsenmeier, R.A. (1993). Oxygen distribution in the macaque retina. Investigative Ophthalmology and Visual Science 34, 516521.
Anderson, B., Jr. (1968). Ocular effects of changes in oxygen and carbon dioxide tension. Transactions of the American Ophthalmology Society 66, 423474.
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, 366370.
Arden, G.B., Sidman, R.L., Arap, W., & Schlingemann, R. (2005). Spare the rod and spoil the eye. British Journal of Ophthalmology 89, 764769.
Arden, G.B., Wolf, J.E., & Tsang, Y. (1998). Does dark adaptation exacerbate diabetic retinopathy? Evidence and a linking hypothesis. Vision Research 38, 17231729.
Bresnick, G.H. (1984). Electroretinographic oscillatory potentials predict progression of diabetic retinopathy. Archives of Ophthalmology 102, 13071311.
Cunha-Vaz, J.G., Fonseca, J.R., de Abreu, J.R.F., & Lima, J.J.P. (1978). Studies on retinal blood flow. II Diabetic retinopathy. Archives of Ophthalmology 96, 809811.
Dawson, W.W., Hazatiwala, K., & Karges, S. (2000). Human photopic response to circulating glucose. Documenta Ophthalmologica 101, 155163.
Dean, F.M., Arden, G.B., & Dornhurst, A. (1997). Partial reversal of protan and tritan colour defects with inhaled oxygen in insulin dependent diabetic subjects. British Journal of Ophthalmology 81, 2730.
Deutsche Ophthalmologische Gesellschaft (2000). Empfehlungen der Deutschen Ophthalmologischen Gesellschaft zur Qualitätssicherung bei sinnesphysiologischen Untersuchungen und Geräten. Der Ophthalmologe 97, 923964.
Drasdo, N., Chiti, Z., Owens, D.R., & North, R.V. (2002). Effect of darkness on inner retinal hypoxia in diabetes: Night-time illumination may be beneficial. Lancet 359, 22512253.
Evans, D.W., Harris, A., Danis, R.P., Arend, O., & Martin, B.J. (1997). Altered retrobulbar vascular reactivity in early diabetic retinopathy. British Journal of Ophthalmology 81, 279282.
Fallon, T.J., Maxwell, D.L., & Kohner, E.M. (1987). Autoregulation of retinal blood flow in diabetic retinopathy measured by blue-light entopic techniques. Ophthalomology 94, 14101415.
Faucher, C. & Kergoat, H. (2002). Modulation of the scotopic electroretinogram and oscillatory potentials with systemic hyperoxia and hypercapnia in humans. Current Eye Research 24, 376386.
Findl, O., Dallinger, S., Rami, B., Polak, K., Schober, E., Wedrich, A., Ries, E., Eichler, H.G., Wolzt, M., & Schmetterer, L. (2000). Ocular haemodynamics and colour contrast sensitivity in patients with type 1 diabetes. British Journal of Ophthalmology 84, 493498.
Fritsche, A., Stefan, N., Hardt, E., Schuetzenauer, S., Haering, H., & Stunmvoll, M. (2000). A novel hyperglycaemic clamp for characterization of islet function in humans: Assessment of three different secretagogues, maximal insulin response and reproducibility. European Journal of Clinical Investigation 30, 411418.
Glocklin, V.C. & Potts, A.M. (1965). The metabolism of retinal pigment epithelium. II Respiration and glycolysis. Investigative Ophthalmology and Visual Science 4, 226234.
Greenstein, V., Sarter, B., Hood, D., Noble, K., & Carr, R. (1990). Hue discrimination and S cone pathways sensitivity in early diabetic retinopathy. Investigative Ophthalmology and Visual Science 31, 10081014.
Grunwald, J.E., DuPont, J., & Riva, C.E. (1996). Retinal haemodynamics in patients wih early diabetes mellitus. British Journal of Ophthalmology 37, 886897.
Grunwald, J.E., Riva, C.E., Brucker, E.J., Sinclair, S.H., & Petrig, B.L. (1984). Altered retinal vascular response to 100% oxygen breathing in diabetes mellitus. Ophthalmology 91, 14471452.
Hall, J.L (1981). Hybrid adaptive procedures for estimation of psychometric functions. Journal of the Acoustical Society of America 69, 17631769.
Hardy, K.J., Scase, M.O., Foster, D.H., & Scarpello, J.H.B. (1995). Effect of short term changes in blood glucose on visual pathway function in insulin dependent diabetes. British Journal of Ophthalmology 79, 3841.
Harris, A., Arend, O., Danis, R.P., Evans, D., Wolf, S., & Martin, B.J. (1998). Hyperoxia improves contrast sensitivity in early diabetes. British Journal of Ophthalmology 80, 209213.
Henson, D.B. & North, R.V. (1979). Dark adaptation in diabetes mellitus. British Journal of Ophthalmology 63, 539541.
Herse, P. (1995). A new method for quantification of the dynamics of dark adaptation. Optometry and Visual Science 72, 907910.
Hoang, Q.V., Linsenmeier, R.A., Chung, C.K., & Curcio, C.A. (2002). Photoreceptor inner segments in monkey and human retina: Mitochondria density, optics and regional variation. Visual Neuroscience 19, 395407.
Kergoat, H. & Tinjust, D. (2004). Neuroretinal function during systemic hyperoxia and hypercapnia in humans. Optometry and Visual Science 81, 214220.
Klemp, K., Larsen, M., Sander, B., Vaag, A., Brockhoff, P.B., & Lund-Andersen, H. (2004). Effect of short-term hyperglycemia on multifocal electroretinogram in diabetic patients without retinopathy. Investigative Ophthalmology and Visual Science 45, 38123819.
Klemp, K., Sander, B., Brockhoff, P.B., Vaag, A., Lund-Anderson, H., & Larsen, M. (2005). The multifocal ERG in diabetic patients without retinopathy during eugenic clamping. Investigative Ophthalmology and Visual Science 46, 26202626.
Kurtenbach, A., Shiefer, U., Neu, A., & Zrenner, E. (1999). Pre-retinopic changes in the colour vision of juvenile diabetics. British Journal of Ophthalmology 83, 4346.
Lakowski, R., Aspinall, P.A., & Kinnear, P.R. (1972/73). Association between colour vision losses and diabetes mellitus. Ophthalmic Research 4, 145159.
Lamb, T.D. & Pugh, E.N. (2004). Dark adaptation and the retinoid cycle of vision. Progress in Retinal Eye Research 12, 307380.
Linsenmeier, R.A. (1986). The effect of light and darkness on oxygen distribution and consumption in the cat retina. Journal of General Physiology 88, 521542.
Mata, N.L., Radu, R.A., Clemmons, R.S., & Travis, G.H. (2002). Isomerization and oxidation of vitamin a in cone-dominant retinas: A novel pathway for visual-pigment regeneration in daylight. Neuron 36, 6980.
McDonald, R. & Adler, F.H. (1939). Effects of anoxia on dark adaptation of normal and of vitamin A deficient subject. Archives of Ophthalmology 22, 980988.
McFarland, R.A. & Evans, J.N. (1939). Alterations in dark adaptation under reduced oxygen tension. American Journal of Physiology 127, 3750.
McFarland, R.A., Halpern, M.H., & Niven, J.I. (1946). Visual thresholds as an index of physiological imbalance during insulin hypoglycaemia. American Journal of Physiology 145, 299313.
Michelson, I.C. (1948). The mode of development of the vascular system of the retina, with some observations on its significance for certain retinal diseases. Transactions of the Opthalmology Society, U.K. 68, 137180.
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, 617624.
Nihira, M., Anderson, K., Gorin, F., & Burns, M. (1995). Primate rod and cone photoreceptors may differ in glucose accessibility. Investigative Ophthalmology and Visual Science 36, 12591270.
North, R.V., Cooney, O., Chambers, D., Dolben, J., & Owens, D.R. (1997). Does hyperglycemia have an influence upon colour vision of patients with diabetes mellitus? Ophthalmic and Physiological Optics 17, 96101.
Schmetterer, L. & Wolzt, M. (1999). Ocular blood flow and associated functional deviations in diabetic retinopathy. Diabetologia 42, 387405.
Schneck, M.E., Fortune, B., Switkes, E., Crognale, M., & Adams, A.J. (1997). Acute effects of blood glucose on chromatic visually evoked potentials in persons with diabetes and in normal persons. Investigative Ophthalmology and Visual Science 38, 80010.
Simonsen, S.E. (1980). The value of the oscillatory potential in selecting juvenile diabetics at risk of developing proliferative retinopathy. Acta Ophthalmologica Scandinavica 58, 865878.
Smith, V.C., Ernest, J.T., & Pokorny, J. (1976). Effect of hypoxia on FM100 hue test performance. Modern Problems in Ophthalmolmology. Colour Vision Deficiencies III 17, 248256.
Stefansson, E. (1990). Oxygen and diabetic eye disease. Graefe's Archives of Clinical and Experimental Ophthalmology 228, 120123.
Stefansson, E., Machemer, R., de Juan, E.J., McCuen, B.W.N., & Peterson, J. (1992). Retinal oxygenation and laser treatment in patients with diabetic retinopathy. American Journal of Ophthalmology 113, 3638.
Volbrecht, V.J., Schneck, M.E., Adams, A.J., Linfoot, J.A., & Ai, E. (1994). Diabetic short-wavelength sensitivity: Variations with induced changes in blood glucose level. Investigative Ophthalmology and Visual Science 35, 243246.
Wang, L., Kondo, M., & Bill, A. (1997). Glucose metabolism in cat outer retina. Investigative Ophthalmology and Visual Science 38, 4855.
Wangsa-Wirawan, N.D. & Linsenmeier, R.A. (2003). Retinal oxygen: Fundamental and clinical aspects. Archives of Ophthalmology 121, 54757.
Williamson, J.R., Chang, K., Frangos, M., Hasan, K.S., Ido, Y., Kawamura, T., Nyengaard, J.R., van den Enden, M., Kilo, C., & Tilton, R.G. (1993). Hyperglycemic pseudohypoxia and diabetic complications. Diabetes 42, 801813.
Wise, G.N. (1956). Retinal neovascularisation. Transactions of the American Ophthalmology Society 54, 729826.
Yu, D.-Y., Cringle, E.S.J., Alder, V.A., & Su, E.N. (1999). Intraretinal oxygen distribution in the rat with graded systemic hyperoxia and hypercapnia. Investigative Ophthalmology and Visual Science 40, 20822087.



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