In vivo models

Two-Stage Laser-Induced Subretinal Fibrosis

In 2020, Little and colleagues presented a two-stage laser-induced mouse model of subretinal fibrosis (Little et al., 2020), modifying the classical single-laser choroidal neovascularization (CNV) (Tobe et al., 1998). In the first stage, laser burns rupture Bruch’s membrane at multiple spots per eye, inducing CNV that typically peaks around Day 5 – Day 7 and begins to regress within three weeks. Before this regression occurs, at Day 7 a second laser burn is applied to each of the original lesions. This second lasering triggers renewed vascular leakage and, mild hemorrhage in a subset of lesions, converting the CNV into a stable fibrovascular membrane.

The resulting lesions recapitulate three hallmark pathological features of neovascular age-related macular degeneration (nAMD): persistent neovascularization, macrophage infiltration, and subretinal fibrosis. Because of this fibrovascular, non-regressing phenotype, the two-stage laser model is a valuable translational tool for dissecting the mechanisms of subretinal fibrosis and for testing the efficacy of anti-fibrotic treatments in nAMD.

See our automated detection of vascular leakage areas

Technical details

Disease indications

Wet AMD

Animal species

Mouse

Method of induction

Diode laser

Route of test article administration

Topical (e.g. eye drops), intravitreal, subretinal, subconjuctival, systemic

Readouts

In vivo imaging:
– Fluorescein angiography (FA)
– Spectral-domain optical coherence tomography (SD-OCT)
Morphological assessment:
– Histology
– Immunohistochemistry
Molecular biology:
– qPCR
– ELISA
– Western blotting
– In situ hybridization/RNAscope