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Elisabeth Richert, Jan Tode, Katharina Vinh, Alexa Karina Klettner, Stefan Otto Johannes Koinzer, Ralph Lucius, Ralf Brinkmann, Johann Roider; Effect of two Laser Treatments on Bruchs Membrane Thickness in a Mouse Model of Age-related Macular Degeneration. Invest. Ophthalmol. Vis. Sci. 2018;59(9):66.
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© ARVO (1962-2015); The Authors (2016-present)
Thickening of Bruchs membrane (BrM) is one of the main characteristics of dry age related macular degeneration. We applied two laser treatments not damaging the neural retina: Selective Retina Therapy (SRT) solely addressing the retinal pigment epithelium (RPE) and Thermal Stimulation of the Retina (TS-R) sublethally is heating the retina/RPE/choroid complex. We compared the effect of SRT and TS-R on BrM thickness in nuclear factor E2-related factor 2 (Nrf2) k.o. mice.
In thirteen 13 month old Nrf2-/- mice one eye was treated with a pulsed SRT laser (532 nm Nd:YAG, pulse duration 250 ns, repetition rate 500 Hz, mean energy 1.8 µJ, duration 300 ms) or TS-R laser (532 nm continous wave, 10 ms duration, mean power 3.3 mW) respectively.The spot size was 50 µm. Fellow eyes were used as untreated controls. We applied an average of 188 laser spots uniformly across the fundus. Energy/Power was chosen 70 % below clinical visibly threshold. Eyes were examined by fundus photography and optical coherence tomography (OCT) at the date of treatment and 1 month later, when eyes were enucleated. BrM thickness was measured by transmission electron microscopy (TEM) in a standardized procedure. Laser induced RPE damage was investigated by scanning electron microscopy (SEM).
In fundus imaging and OCT, Nrf2-/- mice showed AMD-associated degenerative changes (e.g. drusen-like deposits). Laser spots were not visible by fundus imaging or OCT. In SEM, SRT laser spots were visible as discreet RPE lesions without damage of underlying layers. TSR did not produce any RPE lesion. In TEM we observed a trend towards a reduction of BrM thickness after TS-R (mean BrM thickness 597.7 nm ± 105.0 nm vs. control 637.4 ± 138.7). After SRT we observed a significant reduction (p< 0.05) of BrM thickness in laser treated eyes (416.4 nm ± 48.6 nm) compared to untreated fellow eyes (451.9 nm ± 46.5 nm) 1 month after SRT. The observed decrease of BrM thickness in both untreated and SRT treated eyes, compared to TS-R group, might be due to a possible laser induced effect not only to treated eyes but also to intrainduvidual control eyes.
Both laser irradiations reduced BrM thickness in Nrf2-/- mice likely by RPE stimulation and rejuvenation without thermal damage to the neuroretina. This could improve flux of nutrients and oxygen across BrM and might represent a possible treatment for early AMD.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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