Abstract
Purpose: :
To investigate the development of dopaminergic (DAergic) processes in Penn et al.’s (1994) oxygen-induced retinopathy (OIR) "ROP rat." DAergic activity is involved in eye growth and refractive development. The ROP rat eye is characterized by shorter axial length, myopia, and decreased retinal DA content.
Methods: :
ROP and room-air-reared (RAR) control rats were studied at postnatal day (P) 14, 16, 18, 19, 20 and 23. After obtaining dark-adapted electroretinograms (ERGs), eyes were enucleated, fixed, embedded, and frozen for cryosectioning. Retinal cross-sections (16 µm) that included optic-nerve and ora were double-stained against tyrosine hydroxylase (TH, the rate-limiting enzyme in the biosynthesis of DA) with mono- (MAB318; Millipore, Billerica, MA) and polyclonal (AB152; Millipore) antibodies. TH-immunoreactive (TH+) processes in the IPL were quantified (per cross-sectional length) in central and peripheral retina using ImageJ.
Results: :
The two antibodies yielded nearly identical results. At P14, a few TH+ processes were observed at the boundary of the inner nuclear layer (INL) and inner plexiform layer (IPL) in ROP and RAR rats; cell bodies in the INL were weakly stained. In RAR rats, the number of TH+ processes rose steadily with age, appearing also in lamina 3 of the IPL. Cell bodies became heavily stained. However, TH labeling was consistently lighter peripherally, suggesting a central-peripheral gradient in normal DAergic maturation. At P14, the ROP and RAR rats’ TH+ profiles were indistinguishable. Yet in ROP rats, there was no developmental increase in TH labeling, so that the magnitude of the difference between ROP and RAR increased steadily. The developmental course of the ERG oscillatory potentials (OPs) was similar to that of TH in both ROP and RAR.
Conclusions: :
In early post-eye-opening development, DAergic cells' neuronal networks undergo rapid growth, which OIR disrupts. ERG data, particularly OPs (which originate, in large part, in the deeper retinal layers), may imply damage to DAergic cells (which reside in the deeper retinal layers); such damage, if present, may be involved in aberrant eye growth and refractive development. As in this rat model, myopia in ROP occurs in small eyes. Also, the OPs are small in ROP myopia.
Keywords: dopamine • retinopathy of prematurity • development