A role for photoreceptors in retinal oedema and angiogenesis: an additional explanation for laser treatment?
OBJECTIVE
To investigate the possible roles of retinal photoreceptors in macular oedema and retinal angiogenesis with particular reference to the mode of action of laser therapy.


METHODS
(i) Studies in rats made hypoxic for 2 h by administering an oxygen/nitrogen mixture of reduced oxygen content, and growth factors determined by RT-PCR, western blotting, and immunohistochemistry. Assessment of blood-retinal barrier integrity using fluorescent and electron-dense tracers. (ii) Studies in pigs with one retina made hypoxic by selective embolisation of the retinal capillary circulation with fluorescent microspheres. (iii) Assessment of laser therapy in selected cases of retinal neovascularisation indicating a role for photoreceptors.


RESULTS
In the hypoxic retina, angiogenic and vascular permeability factors such as vascular endothelial growth factor (VEGF), nitric oxide synthases (NOSs), and insulin-like growth factor-1 are upregulated in retinal astrocytes and Müller cells but are also present in large amount in the photoreceptors. Hypoxia-inducible factor-1 (HIF-1) is upregulated in retinal glial cells but not in the photoreceptors, suggesting that growth factors in the photoreceptors may not have been generated there. The tracer dye, rhodium isothiocyanate, leaking from an abnormally permeable inner blood-retinal barrier in the hypoxic retina accumulates in the photoreceptors.


CONCLUSIONS
The results indicate that laser treatment of macular oedema or retinal neovascularisation may obtain its effect not only by improving oxygen availability in the inner retina, but also by reducing the load of angiogenic/permeability factors that accumulate in the photoreceptors in hypoxic/ischaemic conditions.
Foulds
W S
WS
Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore. wallace.stewart.foulds@seri.com.sg
Kaur
C
C
Luu
C D
CD
Kek
W K
WK
D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D001813:Blood-Retinal Barrier / Q000473:pathology; D015153:Blotting, Western; D000860:Hypoxia; D051793:Hypoxia-Inducible Factor 1 / Q000378:metabolism; D007150:Immunohistochemistry; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D053685:Laser Therapy; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000503:physiopathology / Q000601:surgery*; D009457:Neuroglia / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D010211:Papilledema / Q000378:metabolism / Q000503:physiopathology / Q000601:surgery*; D020419:Photoreceptor Cells, Vertebrate / Q000378:metabolism*; D051381:Rats; D012160:Retina / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013552:Swine; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D051793:Hypoxia-Inducible Factor 1; D042461:Vascular Endothelial Growth Factor A; D007334:Insulin-Like Growth Factor I; D019001:Nitric Oxide Synthase