Abstract
Retinopathy of prematurity (ROP) is a retinal disease characterized by aberrant vascular and neural development
that affects prematurely born infants receiving supplemental oxygen therapy. Advances in neonatal care enable
physicians to save the lives of increasingly premature infants. However, these infants are at great risk for
developing ROP because the high oxygen levels in neonatal incubators suppress retinal vascular development.
When returned to room air, there is a compensatory pathological neovascularization that results in retinopathy.
Retinal ganglion cell opsins, melanopsin (OPN4) and neuropsin (OPN5), regulate vascular development in the
perinatal period of mice. OPN4 is a blue light-sensitive opsin, while OPN5 is maximally sensitive to visible violet
light. An OPN4-dependent light response pathway has been shown to regulate vascular development in the eye
by keeping VEGFA levels in check (OPN4-VEGFA pathway) (Rao et al., Nature 2013; 494:243-6). OPN5 also
regulates vascular development in the eye. Opn5 null mice show mildly elevated retinal vascular density and
neuron number, and promiscuous hyaloid vessel retraction (Nguyen et al., Nature Cell Biol 2019; 21:420-429).
OPN5 modulates vascular development via dopamine-regulated VEGFR2 expression (OPN5-dopamine-
VEGFR2 pathway). The proposed research will test the hypothesis that stimulation of the OPN4-VEGFA blue
light response pathway will protect retinal vascular development in an oxygen-induced retinopathy (OIR)
mouse model of ROP, while stimulation of the OPN5-dopamine-VEGFR2 violet light pathway will
exacerbate retinopathy. To test of this innovative hypothesis, we propose two specific aims using the mouse
OIR model. In aim 1, we will explore the role of OPN4 manipulation, examining the effects of removing
environmental blue light or enhancing blue light on the severity of retinopathy, using both wildtype and Opn4
mutant mice. In aim 2, we will explore the role of OPN5 manipulation, examining the effects of removing
environmental violet light or enhancing violet light on the severity of retinopathy, using both wildtype and Opn5
mutant mice. Effects of blue light or violet light therapy will be assessed during oxygen treatment (P7-12) and in
the ensuing developmental period (P17-P50). Our findings will have broad implications for prenatal and neonatal
eye care, and may lead to the development of an innovative, non-invasive, light-based preventative treatment
for ROP.