The Protective Effect of Melanopsin on Retinal Vascular Development in a Mouse Model of Retinopathy of Prematurity Restricted; Files Only
Zhang, Huayue (Spring 2024)
Abstract
Importance: Retinopathy of prematurity (ROP) is a vasoproliferative retinal disorder that affects premature infants receiving supplemental oxygen to treat pulmonary insufficiency. It has become a leading cause of childhood blindness as the prevalence of preterm babies has increased in recent decades. Current therapies for ROP, including laser ablation, cryotherapy, and anti-VEGF therapies, have limited efficacy in visual outcomes and significant side effects. Thus, there is a need for alternative therapies that are safe and efficacious.
Purpose: Melanopsin (Opn4) is a blue-light sensitive opsin expressed in melanopsin retinal ganglion cells (mRGCs), which regulate the timing of retinal vascular development. This study was designed to test the hypothesis that the melanopsin light pathway influences the development and severity of oxygen-induced retinopathy (OIR), a mouse model of ROP.
Methods: Experimental groups of Opn4+/+ and Opn4-/- mice were housed in a semi-sealed chamber under an atmosphere of 75-76% O2 from postnatal day P7 to P12, then returned to room air (~22% O2) on P12, where they remained until evaluation. Control-group litters were maintained in room air for the duration of the experiment. Melanopsin activity was modulated by exposure to increasing or omitting blue light from the environment. Retinal vasculature was assessed at P17 and at P50 using retinal flat mounts. Electroretinograms, optical coherence tomography, and visual function were assessed between P42 and P50.
Results: Retinas of oxygen-treated Opn4-/- mice had significantly increased vascular pathology in comparison to Opn4+/- or Opn4+/+ mice when measured at P17 (p<0.01). Scotopic ERG recordings of oxygen-treated Opn4-/- mice showed significantly reduced a-wave amplitudes at flash intensity 10 cd.s/m2 compared to that of Opn4+/+ mice (p<0.05). Oxygen-treated C57BL/6J mice exposed to blue-deficient light from P12-P17 showed greater vascular pathology (p<0.01) compared to colony room light, mimicking the effect of Opn4 knockout. In contrast, blue-enhanced light exposure significantly lowered vaso-obliteration in oxygen-treated Opn4+/+ animals compared to those in colony room light (p=0.01).
Conclusions: Melanopsin deficiency exacerbated the severity of ROP in the OIR mouse model. Blue light stimulation of melanopsin may provide a novel therapeutic approach to influence retinal vasculature development and reduce the severity of ROP.
Table of Contents
Section Page number
I. Introduction 1-9
II. Methods 10-12
III. Results 13-15
IV. Discussion 16-21
V. Table & Figures 22-28
VI. References 29-37
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File download under embargo until 24 May 2026 | 2024-04-14 23:43:57 -0400 | File download under embargo until 24 May 2026 |
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