Abstract
Purpose :
We have previously implicated serine-protease PRSS56 in ocular size determination and PRSS56 variants contribute to both hyperopia and myopia, highlighting its importance in refractive development. Genetic inactivation of Muller glia-derived PRSS56 causes a reduction in ocular axial length/hyperopia. We performed RNA-Seq analysis to identify pathways contributing to PRSS56 mediated ocular growth. We found significant up-regulation of retinal Adamts19 in Prss56-/- as compared to the control mice. Here, we have tested our hypothesis that ADAMTS19 functions downstream of mutant PRSS56 in mediating its effect on ocular size
Methods :
RNA-Seq and qPCR analysis were carried out from total RNA isolated from the retina of Prss56-/- and control Prss56+/- mice (P15). We performed in situ hybridization to localize Adamts19 in the mouse retina. A mouse carrying null alleles of Adamts19 (Adamts19-/-) was generated by βActin-Cre mediated excision of loxP sites flanking exon 3. To determine the combined effect of Prss56 and Adamts19 on ocular size, we generated Prss56-/-; Adamts19-/- (double mutant) mice. A detailed ocular biometric analysis of experimental (single & double mutants) and control groups was performed using the SD-OCT
Results :
By qPCR, we validated the increase in Adamts19 levels observed in the Prss56-/- retina as compared to the controls. Based on in situ hybridization, Adamts19 was detected in the retinal Muller glia of Prss56-/- but not the control (Prss56+/-) retina. The ocular axial length and vitreous chamber depth (VCD) were not significantly different between Adamts19-/-, Adamts19+/- and Adamts19+/+ mice. However, ocular axial length and VCD exhibited a significantly greater reduction in double mutants (Prss56-/-; Adamts19-/-) as compared to Prss56 single mutants (Prss56-/-Adamts19+/-). Overall, our data suggest that the retinal up-regulation of Adamts19 likely compensates for the lack of PRSS56 activity and imparts partial protection against ocular axial length reduction observed in Prss56-/- mice
Conclusions :
Since both PRSS56 and ADAMTS19 belongs to the family of secreted serine-protease and are expressed in the Muller glia, it is likely that they have overlapping function potentially acting on the same substrate. Importantly, our result points toward the existence of a compensatory mechanism in the retina that contributes to ocular axial growth and refractive development
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.