Retina and hypoxia: A “complex couple”

Brughanya S, B.Optom

M.Optom student, Department of Optometry, Medical & Vision Research Foundation, Sankara Nethralaya, Chennai, India

 

Introduction:

• • • Hypoxia is a state of low oxygen tension (refer Figure 1) and is typically associated with abnormal vasculature, which results in a reduced supply of oxygen and nutrients, as well as impaired delivery of drugs ^[1]. Figure 1: Pictorial representation of hypoxia in retina (Image source: Yi, J., Liu, W., Chen, S., Backman, V., Sheibani, N., Sorenson, C. M., Zhang, H. F. (2015). Visible light optical coherence tomography measures retinal oxygen metabolic response to systemic oxygenation. Light: Science & Applications, 4(9), e334-e334.)
  • The retina is the most metabolically active tissue in the human body and, therefore, is highly sensitive to reduction in oxygen tension. Any change in the perfusion pressure of the eye affects the retina although the eye is able to make hemodynamic auto-regulation (refer Figure 2) ^[1]. This justifies that, they express a complex relationship with one another.
    Figure 2: Pictorial representation of hemodynamic auto-regulation of retina to change in perfusion pressure of blood flow.(Image source: Lange, C.A., & Bainbridge, J.W. (2011). Oxygen Sensing in Retinal Health and Disease. Ophthalmologica, 227, 115 – 131.)

Role of oxygen:

Oxygen plays the key role in stabilizing Hypoxic inducible factors (HIF-1α) and its function. When the oxygen tension is normal, HIF-1α is rapidly oxidized by hydroxylase enzymes, but when cells become hypoxic, HIF-1α escapes the degradation and starts to accumulate, triggering the activation of a large number of genes, like vascular endothelial growth factor (VEGF) and erythropoietin ^[1].

Vascular Endothelial Growth Factor:

Vascular endothelial growth factor (VEGF) is regarded as the primary factor in promoting angiogenesis throughout the human body and especially in the retina, where it stimulates the breakdown of the blood retina barrier ^[1].

Erythropoietin:

Erythropoietin (EPO) is an oxygen-regulated glycoprotein and a hematopoietic cytokine that stimulates the proliferation, survival, and differentiation of erythroid stem cells in the bone marrow. EPO is mainly produced in kidneys and also produced in the retina in response to acute hypoxia via HIF-1αstabilization ^[1].

Association between ocular disease and hypoxia:

Diabetic retinopathy:

Decreased blood flow is one of the first physiological signs observed after the onset of diabetes. In the hypoxic state, the retina produces growth factors that regulate vessel leakage into the retina and the vitreous space and angiogenesis, causing fibro vascular tissue formation with the risk of contraction, retinal ablation, and finally loss of vision^[1].

Retinopathy of prematurity(ROP):

ROP is initiated with delayed retinal vascular growth and insufficient vascularisation after premature birth, which creates hypoxia and triggers the release of growth factors leading to abnormal vessel growth in the hypoxic developing retina, VEGF is released and plays a mediating role in neovascularisation ^[1].

Glaucoma:

Tissue hypoxia in the optic nerve head and/or retina is thought to develop secondary to the elevated intraocular pressure in glaucomatous eyes and has been proposed to be associated with pathogenic mechanisms underlying optic nerve degeneration in glaucoma ^[2].

Retinal vein occlusion:

Ischemia-induced hypoxia elicits retinal neovascularisation and is a major component of several blinding retinopathies such as RO, DR and RVO ^[3].

High altitude retinopathy:

As hypoxia increases with higher altitude, arterial oxygen saturation and ocular perfusion pressure are decreased, retinal venous pressure increased, intra-ocular pressure remains stable ^[4].

Visual function changes due to hypoxia:

Hypoxia will have a direct impairment on visual functions such as:

• Colour vision^[4]
• Visual acuity^[5]
• Visual field ^[5]

Conclusion:

It is postulated that a balance between damaging and protective factors exists in the retina at early time intervals after hypoxia. This balance may be disturbed in the long run, leading to hypoxic damage to the retina and neovascularisation. Oxygen deprivation might hamper the visual performance and hence, maintaining a stable oxygen concentration level within the normal range is really important. Any deprivation or abundance in oxygen concentration might result in an alarming condition as mentioned above. This justifies that retina and hypoxia is a complex couple.    

 

                                    

References:

1) Arjamaa, O., &Nikinmaa, M. (2006). Oxygen-dependent diseases in the retina: role of hypoxia-inducible factors. Experimental eye research, 83(3), 473-483.

2) Tezel, G., & Wax, M. B. (2004). Hypoxia-inducible factor 1α in the glaucomatous retina and OpticNerve head. Archives of ophthalmology, 122(9), 1348-1356.

3) Uddin, M. I., Evans, S. M., Craft, J. R., Capozzi, M. E., McCollum, G. W., Yang, R., … & Penn, J. S. (2016). In vivo imaging of retinal hypoxia in a model of oxygen-induced retinopathy. Scientific reports, 6, 31011.

4) Vingrys, A. J., & Garner, L. F. (1987). The effect of a moderate level of hypoxia on human color vision. Documentaophthalmologica, 66(2), 171-185.

5) Groenendaal, F., Van Hof-van Duin, J., Baerts, W., & Fetter, W. P. F. (1989). Effects of perinatal hypoxia on visual development during the first year of (corrected) age. Early human development, 20(3-4), 267-279.