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Quan Findlay, Andrew Ian Jobling, Kirstan Anne Vessey, Ursula Greferath, Pavan Avula, Ben Gu, Robyn H Guymer, Erica L Fletcher; The local and systemic effects following subthreshold nanosecond laser treatment to the posterior retina. Invest. Ophthalmol. Vis. Sci. 2019;60(9):364.
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Recently, a randomized clinical trial of a nanosecond laser showed promising results for reducing progression in some people with Age-related Macular Degeneration (AMD). Here, we investigate the retinal and systemic response to nanosecond laser treatment in mice and individuals with intermediate AMD in order to explore the mechanism(s) of action.
Local effects of nanosecond laser (Ellex, 2RT 532nm, 3ns) treatment (10 laser spots in left eye at 0.065mJ) on retinal pigmented epithelium (RPE) cell division were investigated in C57BL6J mice using BrdU. Eyes were removed and examined at 1, 3, 7, and 14 days post-laser treatment. RPE from 12-month-old ApoEnull (animal model of AMD) and wild type animals were isolated 3 months post laser treatment and a qPCR array performed on genes involved in ageing. Systemic effects of nanosecond laser treatment were examined 3 months post treatment by measuring phagocytosis in peripheral blood monocyte cells (PBMCs) using flow cytometry. PBMCs were isolated from 12-month-old C57BL6J mice and also from patients with intermediate AMD.
Following nanosecond laser treatment, BrdU labelling of RPE cells within the treated area peaked after 3 days (6.5 ± 0.9 cells per laser lesion). Additionally, BrdU labelling of RPE cells in both the non-treated area of the lasered eye and in the fellow untreated eye were seen to be significantly increased at days 7 and 14 (p<0.001). Cell density in a circular area (200 μm diameter) surrounding the centre of the lasered area also showed a significant increase at days 3-14 (p<0.001). ApoEnull untreated animals showed dysregulation of 28 ageing-related genes, while treatment with the nanosecond laser restored the expression of 89% of these genes to wild type levels. Finally, the phagocytic function of PBMCs in both aged mice and patients with intermediate AMD was altered 3 months after nanosecond laser treatment.
The nanosecond laser induces proliferation in the RPE in both the treated and untreated fellow eye suggesting a regenerative response. This laser also produced a reduction in the number of altered ageing genes within the RPE. Systemic effects of the nanosecond laser on circulating monocytes may account for the effects observed in the fellow (untreated) eye. The clinical benefits of nanosecond laser observed in AMD patients may be via systemic modulation of RPE regeneration.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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