Selective Retina Therapy Reduces Bruch's Membrane Thickness and Retinal Pigment Epithelium Pathology in Age-Related Macular Degeneration Mouse Models

Jan Tode; Elisabeth Richert; Stefan Koinzer; Alexa Klettner; Claus von der Burchard; Ralf Brinkmann; Ralph Lucius; Johann Roider

doi:10.1167/tvst.8.6.11

Selective Retina Therapy Reduces Bruch's Membrane Thickness and Retinal Pigment Epithelium Pathology in Age-Related Macular Degeneration Mouse Models

Transl Vis Sci Technol. 2019 Nov 13;8(6):11. doi: 10.1167/tvst.8.6.11. eCollection 2019 Nov.

Authors

Jan Tode¹, Elisabeth Richert¹, Stefan Koinzer¹, Alexa Klettner¹, Claus von der Burchard¹, Ralf Brinkmann², Ralph Lucius³, Johann Roider¹

Affiliations

¹ Christian-Albrechts-University of Kiel, University Medical Center, Department of Ophthalmology, Arnold-Heller-Str. 3, Kiel, Germany.
² Institute for Biomedical Optics, University of Lübeck and Medical Laser Center Lübeck GmbH, Peter-Monnik-Weg 4, Lübeck, Germany.
³ Christian-Albrechts-University of Kiel, Institute of Anatomy, Olshausenstr. 40, Kiel, Germany.

Abstract

Purpose: To investigate the effect of selective retina therapy (SRT) on age-related macular degeneration (AMD)-like alterations of retinal pigment epithelium (RPE) and Bruch's membrane (BrM) in AMD mouse models as therapeutic approach for the treatment of dry AMD.

Methods: In B6.129P2-Apoe^tm1Unc /J (ApoE^-/-) and B6.129X1-Nfe2I2 ^tm1Ywk /J (NRF2^-/-), one randomized eye of each mouse in groups of 15 mice was treated by SRT (532 nm, 300 ms, ∼1.4-μs pulse, 100 Hz, 50-μm spot), the fellow eye and healthy C57BL/6J mice served as controls. Clinical examinations were obtained at treatment day and 1 month later, followed by enucleation to analyze BrM thickness and ultrastructural RPE morphology.

Results: Nearly all ApoE^-/- and NRF2^-/- mice showed AMD-like retinal alterations. BrM thickness was increased in both mouse models, RPE had vacuoles within the cell body and shortened apical microvilli. SRT neither affected neuroretinal anatomy nor function. BrM thickness as well as AMD-like ultrastructural alterations of the RPE were significantly reduced in laser-treated eyes compared with fellow control and untreated control eyes.

Conclusions: SRT reduces BrM thickness and AMD-like RPE alterations in AMD mouse models without damage to structural or functional properties of neuroretina. It may be a prophylactic or therapeutic option for dry AMD.

Translational relevance: SRT shows therapeutic effectivity in murine AMD models and might therefore become an option for the treatment of dry AMD.

Keywords: RPE morphology; drusen; dry AMD; selective retina therapy (SRT); subthreshold laser therapy.