Abstract
Purpose: :
Hyperoxia may arrest retinal vascular development. At the resulting border between vascularized and avascular retina, a thickened hypercellular ridge may appear (Stage 2 Retinopathy of prematurity, or ROP). The ridge is a critical site for either progression to extraretinal neovascularization (Stage 3 ROP) or continued retinal vascularization (regression). Definitive identification of ridge cells is lacking, perhaps due to the rarity of pathological specimens. Here we characterize the ridge using markers for known inner retinal cell types.
Methods: :
Both eyes were obtained at autopsy from a patient born at 28 weeks gestation and clinically diagnosed with stage 2 ROP. The eyes were formalin-fixed, paraffin-embedded, and sectioned at 5 um. Sections were immunohistochemically labeled with markers for mature astrocytes (GFAP), astrocyte precursor cells (PAX-2), vascular endothelial cells (CD31), smooth muscle cells (desmin), and neurons (neuron-specific enolase, or NSE); Ki-67 was used to identify proliferating cells.
Results: :
Cells within the ridge labeled intensely though non-specifically with PAX-2. Variable GFAP labeling occurred in the ridge as well. CD31, NSE and desmin failed to label cells within the ridge. A few scattered ridge cells were positive for Ki-67, which also labeled far peripheral outer retinal cells and endothelial cells in small extraretinal vascular tufts.
Conclusions: :
These results demonstrate that the ridge in Stage 2 ROP is glial, and is composed of a mixture of mature and immature astrocytes; a small microglial contribution is not yet excluded. The surprising paucity of proliferating cells in the ridge may indicate that either (1) the ridge forms by accumulation of astrocyte precursors whose outward migration is halted; or, (2) proliferation occurs in an earlier stage of ridge formation, prior to the age of this specimen.
Keywords: retinopathy of prematurity • astrocyte • retinal development