Purchase this article with an account.
Alexander I. Son, Margaret A. Cooper, Yuhai Sun, Norman J. Kleiman, Renping Zhou; Development of Persistent Hyperplastic Primary Vitreous in Ephrin-A5-/- Mice. Invest. Ophthalmol. Vis. Sci. 2012;53(14):2547.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
The primary vitreous is a collection of cells appearing early in ocular development and occupying the region which will eventually become the vitreous humor. These cells evolve into the hyaloid vasculature, the circulatory network for supplying nutrients and removing metabolic waste in the developing mammalian eye. After birth, the hyaloid vasculature regresses to allow unimpeded light passage to the retina. Failure to regress results in severe consequences, the most notable of which is the development of the pathology Persistent Hyperplastic Primary Vitreous (PHPV). This condition is characterized by the presence of a large retrolental fibrous mass, sometime accompanied by other developmental ocular defects and usually associated with visual disability and/or blindness. Although the condition has been described for more than 50 years, the mechanisms underlying primary vitreous regression remain poorly understood. We have recently found that mice lacking the A-class ligand ephrin-A5 develop hallmark symptoms of PHPV. Thus, expression of the Eph family of receptor tyrosine kinases is essential role to the regression of the primary vitreous and hyaloid vasculature. In the present study, we characterize the nature of PHPV in ephrin-A5-/- mice.
Wild-type and ephrin-A5-/- eyes were examined at various developmental stages to determine the progression of PHPV. Eye tissue was sectioned and examined by H&E staining. Protein expression and localization was determined through immunohistochemistry. Relative levels of Eph receptors were determined by RT-PCR.
Ephrin-A5-/- mice develop a large pigmented mass attached to the retina posterior to the lens. In contrast to wild-type eyes, where cells of the primary vitreous regress by birth, primary vitreous cells in the ephrin-A5-/- mice persist throughout their lifetime. In these animals a hyperplastic mass consisting of neural crest-derived pigmented cells is noted encapsulating the hyaloid vasculature. These cells are mitotically active in the adult ephrin-A5-/- mouse. Eph receptor expression is observed throughout the mass at postnatal stages. Ephrin-A5 expression is observed throughout the eye but not within the developing primary vitreous.
These findings identify ephrin-A5 to be essential to the regression of the primary vitreous in a non-cell-autonomous manner. Absence of ephrin-A5 results in the failed regression of the primary vitreous and resultant continued presence of the hyaloid vasculature. Loss of ephrin-A5 expression may also contribute to associated or subsequent ocular pathologies.
This PDF is available to Subscribers Only