Neurosensory Alterations in Retinopathy of Prematurity: A Window to Neurological Impairments Associated to Preterm Birth

Abstract

Retinopathy of prematurity (ROP) is one of the main blinding diseases affecting preterm newborns and is classically considered a vascular disorder. The premature exposure to the extrauterine environment, which is hyperoxic in respect to the intrauterine environment, triggers a cascade of events leading to retinal ischemia which, in turn, makes the retina hypoxic thus setting off angiogenic processes. However, many children with a history of ROP show persistent vision impairment, and there is evidence of an association between ROP and neurosensory disabilities. This is not surprising given the strict relationship between neuronal function and an adequate blood supply. In the present work, we revised literature data evidencing to what extent ROP can be considered a neurodegenerative disease, also taking advantage from data obtained in preclinical models of ROP. The involvement of different retinal cell populations in triggering the neuronal damage in ROP was described along with the neurological outcomes associated to ROP. The situation of ROP in Italy was assessed as well.

Propranolol: a new pharmacologic approach to counter retinopathy of prematurity progression

“…Since ROP is a disorder of the developing retina, it's quite reasonable to state that it affects the neural retina as well: the vascular and the neural retina are exposed to the same growth factors, proliferating and differentiating in close contact with each other and influencing themselves. Indeed, associations between severe ROP and altered functioning of rods and cones, as well as degeneration of retinal ganglion cells, bipolar and amacrine cells, and decrement of their density have been reported in several studies ( 37 ). Furthermore, since some of the growth factors involved in the development of the retina such as VEGF and IGF-1 act as well on the developing brain, their dysregulation seen in ROP may affect the development of some cerebral regions, determining injury to both the visual axis and other cerebral areas involving motor and cognitive skills.…”

“…Although ROP has been classically described as a vasoproliferative disorder, several findings suggest that it should be considered rather as a neurovascular disease ( 37 ). Visual impairments or even visual loss observed in preterm infants with previous ROP have been generally attributed to macular injury and other ocular complications (such as retinal detachment, and glaucoma) resulting from fibrovascular changes.…”

Retinopathy of Prematurity—Targeting Hypoxic and Redox Signaling Pathways

“…During physiological retinal angiogenesis, blood vessels begin to form around the 14-15th week of gestation, originating from the optic nerve head and expanding centrifugally towards the retinal periphery [82]. By 36 weeks of gestation, the nasal portion of the retina becomes vascularized, while the temporal area completes this process by the 40th week.…”

Treating infants with 0.2% propranolol eye micro‐drops drastically reduced the progression of retinopathy of prematurity

“…Retinopathy of prematurity is predominantly considered a proliferative vascular disease. However, persistent vision impairments due to photoreceptors and post‐receptor retinal neuron disorders observed in patients who had ROP suggest associations with neurosensory alterations 5 . Therefore, the availability of a drug with high cerebrospinal fluid permeability that interrupts the progression of ROP, protects retinal cells and prevents astrocyte degeneration 5 could provide neuroprotection.…”