A micropulse laser-induced non-human primate photoreceptor injury model for the study of retinal degenerations

Abstract

Purpose : Retinal degenerations are a heterogenous group of conditions which differ in pathophysiology but are characterised by the demise of photoreceptors. The non-human primate (NHP) model is important for such studies due to the presence of an anatomical macula, which is not seen in other animals. While there have been attempts to create NHP models using systemic or intravitreal delivery of retinotoxic agents, these are associated with increased systemic complications and uncontrollable distribution of retinal lesions.

Ophthalmic lasers are useful for creating animal models of retinal diseases. As compared to the traditional argon laser, the micropulse (MP) laser delivers lower energy but repetitive series of short pulses. This may allow selective and consistent destruction of photoreceptors without damaging the Bruch’s membrane. Thus, it may avoid choroidal neovascularisation (CNV) which has a different pathogenesis. In this abstract, we investigate the utility of the MP laser in creating a NHP model of degenerative retinal diseases.

Methods : A Macaca fascicularis was used to create the RD model using the IQ 532 Micropulse Laser (Iridex) with a TxCell scanning laser delivery device and a Volk HR centralis contact lens (Volk Optical Inc) with a 74° degree field of view. 4 settings were tested for their ability to cause selective photoreceptor damage:
A: 66J/m² Fluence: Duty cycles of 2% (0.2ms pulse “on”, 9.8ms pulse “off”), Power 2000mW
B: 33J/m² Fluence: Duty cycles of 1% (0.1ms pulse “on”, 9.0ms pulse “off”), Power 2000mW
C: 49.5J/m² Fluence: Duty cycles of 1.5% (0.15ms pulse “on”, 9.8ms pulse “off”), Power 2000mW
D: 37.125J/m² Fluence: Duty cycles of 1.5% (0.15ms pulse “on”, 9.8ms pulse “off”), Power 1500mW
Optical coherence tomography and autofluorescence of the macula were done on Day 0, 7 and 20 from the initial procedure. Histological analysis was done after 20 days.

Results : Of the 4 settings, Settings A, C and D were able to achieve photoreceptor damage reflected on imaging. Only Setting A was associated with CNV development after 20 days. Photoreceptor damage was not achieved with Setting B.

Conclusions : At specific settings, the MP laser can potentially be used for the creation of a NHP model of RD. Further investigations including electroretinography and transcriptional analyses are required for validation of this model.

This is a 2021 ARVO Annual Meeting abstract.