Retinoscleral control of scleral remodelling in refractive development: a role for endogenous FGF-2?
OBJECTIVE
Studies in avian models of myopia have shown that refractive error development can be influenced by exogenously delivered fibroblast growth factor (FGF)-2. The present study sought to determine whether endogenous FGF-2 was associated with retinoscleral signalling or scleral remodelling during changes in refractive error in a mammalian model of myopia.


METHODS
Myopia was induced in tree shrews over a 5-day period. One group of animals was then allowed 3 days of recovery from the induced myopia. Endogenous levels of FGF-2 were measured in scleral and retinal homogenates using ELISA. Real-time PCR was used to investigate scleral FGF-2 and FGF receptor (FGFR)-1 mRNA expression.


RESULTS
No difference in FGF-2 content was found in posterior scleral or retinal extracts of myopic eyes (scleral -4+/-9%, retinal +23+/-17%) or recovering eyes (scleral -10+/-18%, retinal +1+/-13%), when compared with contralateral control eyes. In addition, no significant changes were found in scleral FGF-2 mRNA expression in myopic or recovering eyes (+106+/-56% and +14+/-12% respectively, P=0.21). However, FGF-2 concentration was significantly higher in anterior, relative to posterior, scleral regions in all animals (1602+/-105 vs 1030+/-50pg/mg respectively P<0.001). Expression of scleral FGFR-1 mRNA was upregulated in myopic eyes (+186+/-32%, P=0.01) but returned to control eye levels during recovery (+63+/-20%).


CONCLUSIONS
The findings indicate that alterations in endogenous retinal or scleral FGF-2 levels are not associated with changes in scleral remodelling in this mammalian model of myopia. However, the reversible changes found in FGFR-1 expression in the sclera of myopic eyes mean that an indirect role for FGF-2 in the control of scleral remodelling is implicated. The anteroposterior difference found in scleral FGF-2 concentration indicates a role for this cytokine in the control of normal scleral growth and development and, presumably, eye size.
Gentle
Alex
A
Department of Optometry and Vision Sciences, The University of Melbourne, Victoria 3010, Australia.
McBrien
Neville A
NA
D000818:Animals; D004797:Enzyme-Linked Immunosorbent Assay; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism* / Q000502:physiology*; D009216:Myopia / Q000378:metabolism* / Q000628:therapy*; D012333:RNA, Messenger / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000096:biosynthesis; D051496:Receptor, Fibroblast Growth Factor, Type 1; D017468:Receptors, Fibroblast Growth Factor / Q000096:biosynthesis; D012160:Retina / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012590:Sclera / Q000378:metabolism / Q000473:pathology*; D012788:Shrews; D013997:Time Factors
D012333:RNA, Messenger; D017468:Receptors, Fibroblast Growth Factor; D016222:Fibroblast Growth Factor 2; D020794:Receptor Protein-Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1