June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Persistent activity of Muller glia-derived PRSS56 is required for refractive development
Author Affiliations & Notes
  • Seyyedhassan Paylakhi
    Ophthalmology, University of California, San Francisco (UCSF), San Francisco, California, United States
  • Cassandre Labelle-Dumais
    Ophthalmology, University of California, San Francisco (UCSF), San Francisco, California, United States
  • Yusef Seymens
    City College of San Francisco, San Francisco, California, United States
  • Nair Kayarat Saidas
    Ophthalmology, University of California, San Francisco (UCSF), San Francisco, California, United States
  • Footnotes
    Commercial Relationships   Seyyedhassan Paylakhi, None; Cassandre Labelle-Dumais, None; Yusef Seymens, None; Nair Kayarat Saidas, None
  • Footnotes
    Support  This work was supported in part NIH P30 core grant for vision research (UCSF, Ophthalmology), Research to Prevent Blindness unrestricted grant (UCSF Ophthalmology) and Special Scholar award (KSN), and NEI grants EY022891 (KSN), That man may see (KSN), Research Evaluation and Allocation Committee (REAC)-Tidemann fund (KSN), Marin Community Foundation- Kathlyn McPherson Masneri and Arno P. Masneri Fund (KSN), KTEF Career-Starter Research Grant (SP).
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 5635. doi:
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      Seyyedhassan Paylakhi, Cassandre Labelle-Dumais, Yusef Seymens, Nair Kayarat Saidas; Persistent activity of Muller glia-derived PRSS56 is required for refractive development. Invest. Ophthalmol. Vis. Sci. 2017;58(8):5635.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Ocular axial growth is central to refractive development. Alteration in ocular axial length leads to refractive errors. Molecular factors governing ocular growth are poorly defined. We have previously implicated a serine protease, PRSS56, in ocular axial growth and their genetic variants are implicated in refractive errors. Here, combinations of genetic mouse models were utilized to study the role of PRSS56 in the ocular axial growth.

Methods : Ocular expression of Prss56 was determined by lineage-tracing and in situ hybridization. Conditional Prss56 mutant (Prss56fl) mice were generated to delineate the spatiotemporal requirements of Prss56 on ocular growth. An inducible Rax-Cre ERt2 was used to ablate Prss56 from retinal Muller glia following tamoxifen injection at P8. Ubiquitous inducible Ubc-Cre line was used to ablate Prss56 (Prss56fl/fl;Ubc-Cre ERt2) during distinct stages, both before [Postnatal (P) days 6, and 8] and after opening of the eye (at P13). Optical Coherence Tomography was employed to perform ocular biometry, including axial length (AL) measurements starting from P5 to P60. Mouse auto-photorefractor was employed to measure the ocular refraction.

Results : Prss56 is first detected in the late retinal progenitor cells, and in a subset of Muller glial cells following retinal cell differentiation. Prss56-/- eyes display a reduced ocular axial length starting at P5 compared to the controls (Prss56+/- or Prss56+/+) and subsequently develop hyperopia. Conditional ablation of Prss56 specifically from differentiated Muller glia by inducing activation of Rax-Cre ERt2 caused a significant reduction in ocular axial length as compared to control groups (2.724±0.036 mm for Prss56fl/fl vs 2.869±0.0164 mm for Prss56fl/+, p<0.001). Stage-specific ablation of Prss56 both before (P6 and P8) and following the opening of the eyes (P13) caused reduction in AL compared to the controls. Prss56 ablation at an earlier time point (P6) caused a greater reduction in AL compared to later ablation at P8 (0.115± 0.027 mm at P6 vs 0.08±0.02 at P8).

Conclusions : PRSS56 derived from Muller glia contributes to ocular growth in a stage-specific manner. Persistent activity of PRSS56 both before (prevision) and following the opening of the eyes is required to sustain ocular axial growth. Thus, we identify a factor that operates in a continuum through distinct stages to support ocular growth and normal refractive development.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

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