Abstract
Purpose::
Regulation of TGF-ß isoforms are implicated in scleral remodeling in myopia. It has been previously reported that down-regulation of scleral TGF-ß occurs before and during measurable changes in eye size. The purpose of this study was to determine retinal and choroidal TGF-ß isoform regulation during myopia induction.
Methods::
Myopia was induced in tree shrews by monocular deprivation of form-vision. Retinal and choroidal TGF-ß isoform mRNA expression was determined at 24 hours and 5 days after initiation of myopia induction, using quantitative real-time PCR. Retinal TGF-ß2 protein (active and latent forms) was quantified by ELISA.
Results::
mRNA for all three mammalian isoforms were expressed in the tree shrew retina, with TGF-ß2 the predominant isoform (TGF-ß1:ß2:ß3 ratio, 27:333:1). All three isoforms showed no significant changes in retinal mRNA levels between the treated and contralateral control eyes at both 24 hours (TGF-ß1: 5±6%, p=0.48; TGF-ß2: -20±9%, p=0.08; TGF-ß3: 6±8%, p=0.54; mean±SEM) and 5 days (TGF-ß1: 9±16%, p=0.61; TGF-ß2: 16±18%, p=0.40; TGF-ß3: -10±12%, p=0.43) of myopia induction. Similar to retina, no significant changes in the mRNA expression level of the three isoforms were found in the choroid. Reflecting the gene data, the amount of total TGF-ß2 protein in tree shrew retina (224±48 pg/mg of total protein) remained unchanged between the treated and contralateral control eyes at 24 hours and 5 days of myopia induction. However, the active/latent ratio of TGF-ß2 protein underwent a significant reduction (-40±10%, p<0.05) at 5 days of myopia induction due to decreased active TGF-ß2 protein. No differences were observed at mRNA and total TGF-ß2 protein levels in control eyes between 24 hours and 5 days of myopia induction.
Conclusions::
While all three mammalian TGF-ß isoforms are expressed in tree shrew retina and choroid, no significant changes in isoform mRNA expression were found in the retina or choroid at either 24 hours or 5 days of myopia induction. The reduction in TGF-ß2 active protein at 5 days may be important in the ocular remodeling observed during myopic eye growth.
Keywords: myopia • retina • growth factors/growth factor receptors