title: Retinal and choroidal TGF-beta in the tree shrew model of myopia: isoform expression, activation and effects on function.
abstract: A visually evoked signalling cascade, which begins in the retina, transverses the choroid, and mediates scleral remodelling, is considered to control eye growth. The ubiquitous cytokine TGF-beta has been associated with alterations in ocular growth, where alterations in scleral TGF-beta isoforms mediate the scleral remodelling that results in myopia. However, while the TGF-beta isoforms have been implicated in the scleral change during myopia development, it is unclear whether alterations in retinal and choroidal isoforms constitute part of the retinoscleral cascade. This study characterised the retinal and choroidal TGF-beta isoform profiles and TGF-beta2 activation during different stages of myopia development, as induced by form deprivation, in a mammalian model of eye growth. Using quantitative real-time PCR, the mRNA for all three mammalian isoforms of TGF-beta was detected in tree shrew retina and choroid. Distinct tissue-specific isoform profiles were observed for the retina (TGF-beta1:TGF-beta2:TGF-beta3=20:2085:1) and choroid (TGF-beta1:TGF-beta2:TGF-beta3=16:23:1), which remained constant over the development period under investigation. The active and latent pools of retinal TGF-beta2 were quantified using ELISA with the majority (>94%) of total TGF-beta2 found in the latent form. Unlike previous scleral data showing early and continuous decreases in TGF-beta isoform expression during myopia development, the levels of the three isoforms remained within normal ranges for retinal (TGF-beta1, -14 to +14%; TGF-beta2, -2 to +20%; TGF-beta3, -10 to +26%) and choroidal (TGF-beta1, -19 to +21%; TGF-beta2, -26 to +8%; TGF-beta3, -11 to +28%) tissues during myopia development (induction times of 3h, 7h, 11h, 24h, and 5 days). A 40% decrease in retinal TGF-beta2 activation was observed after 5 days of myopia development, however, there was no functional correlate of altered TGF-beta2 activity, as assessed by the retinal ERG response. Overall, these data highlight the specific nature of TGF-beta isoform expression, which reflects the differences in tissue structure and function. While TGF-beta isoforms are involved in scleral regulation during myopia development in mammals, they do not have a primary role in the retinal and choroidal signals. Thus, the regulation of eye growth via the retinoscleral cascade involves more than one factor, which is likely to be tissue-specific in nature.
authors.affiliation: Department of Optometry and Vision Sciences, The University of Melbourne, Parkville, Melbourne, Victoria, Australia.
authors.forename: Andrew Ian
authors.initials: AI
authors.lastname: Jobling
authors.forename: Ran
authors.initials: R
authors.lastname: Wan
authors.forename: Alex
authors.initials: A
authors.lastname: Gentle
authors.forename: Bang Viet
authors.initials: BV
authors.lastname: Bui
authors.forename: Neville Anthony
authors.initials: NA
authors.lastname: McBrien
mesh_terms: D000818:Animals; D002829:Choroid / Q000378:metabolism*; D004195:Disease Models, Animal; D018450:Disease Progression; D004596:Electroretinography / Q000379:methods; D005136:Eye Proteins / Q000378:metabolism; D015870:Gene Expression; D009216:Myopia / Q000378:metabolism* / Q000503:physiopathology; D020033:Protein Isoforms / Q000378:metabolism; D012160:Retina / Q000378:metabolism* / Q000503:physiopathology; D016212:Transforming Growth Factor beta / Q000378:metabolism* / Q000502:physiology; D053781:Transforming Growth Factor beta2 / Q000378:metabolism; D014418:Tupaiidae
chemical_list: D005136:Eye Proteins; D020033:Protein Isoforms; D016212:Transforming Growth Factor beta; D053781:Transforming Growth Factor beta2