Abstract
Purpose :
Inflammatory processes play a major role in pathogenesis and disease progression of multifactorial age-related macular degeneration (AMD). Anti-inflammatory therapies have not shown therapeutic efficacy so far. Subthreshold laser therapies have proven to be beneficial in treating morphological AMD-like alterations in mice. We analyzed the effect of TSR and SRT on inflammatory processes in AMD mouse models.
Methods :
We investigated 2 mouse models (12 months old nuclear-factor-E2-related factor 2 (NRF2-/-) and 8 months old apolipoprotein E (ApoE-/-) knock-out mice), treated with 2 different laser modalities (TSR (continuous wave laser, 10 ms duration, ~ 4 mW power) and SRT (pulsed laser, 1.4 µs pulse length, 100 Hz frequency, 300 ms duration, ~ 2.2 µJ energy)), examined at 2 different time-points (day 1 and day 7 after treatment). 5 eyes of 5 mice each group were treated with ~190 spots of 50 µm size, uniformly applied to the fundus at 30 % power/energy level of individually titrated just visible laser burns. Fellow eyes and untreated mice were controls. Funduscopy and optical coherence tomography (OCT) at treatment day were repeated at day 1 or 7 after treatment and followed by enucleation for PCR-array of 84 inflammation cell-mediators.
Results :
Laser treatment never induced neuroretinal damage. In NRF2-/- and ApoE-/- eyes pro-inflammatory and chemotactic cell mediators were upregulated compared with wild type BL/6J mice. Comparing lasered with untreated eyes, after TSR an initial downregulation of pro-inflammatory chemokines and interleukins at day 1 was followed by an upregulation of chemokines at day 7. In contrast, after SRT an initial upregulation of toll-like receptors, pro-inflammatory chemokines and interleukins was followed by a downregulation of chemokines at day 7.
Conclusions :
TSR and SRT have contrary effects on inflammatory processes. TSR leads to a downregulation of inflammation as initial response to thermal elevation in retinal pigment epithelial (RPE) cells, followed by chemotactic processes. This might reflect delayed apoptotic RPE cell death. SRT leads to an initial pro-inflammatory response induced by instant selective RPE cell disruption. This is seen in necrosis. It remains unclear if these effects are a possible therapeutic component for the treatment of AMD or a parainflammatory consequence of laser treatment itself.
This is a 2020 ARVO Annual Meeting abstract.