Identification of Kinome Biomarkers and Therapeutic Rescue in cGMP-Linked Retinal Degeneration
- 1Sabanci University Nanotechnology Research and Application Center, Istanbul, Turkey
Abstract
Inherited retinal degenerations, such as Retinitis Pigmentosa (RP) and Leber's congenital amaurosis (LCA), are major causes of progressive and irreversible vision loss. The large number of genes associated with these disorders makes their clinical and molecular characterization difficult, while systemic biomarkers for disease progression or treatment response remain limited. These challenges were addressed by targeting cGMP-associated mechanisms shared by RP and LCA and integrating systemic biomarker profiling with retinal outcomes. Kinase activity analysis (kinome analysis) in peripheral blood mononuclear cells distinguished healthy and diseased states and captured therapy-associated signatures in rd10 mice treated with LP-CN03, a liposomal formulation of the cGMP analog CN03. This first systemic analysis in a therapeutically responsive animal model highlights kinome analysis as a potential translational readout. Given shared cGMP signaling in RP and AIPL1-associated LCA, LP-CN03's therapeutic potential was further evaluated in a new CRISPR-Cas9-generated Aipl1-/- mouse model. Treatment with LP-CN03 preserved retinal structure and function, as shown by electroretinography, longitudinal optical coherence tomography, fundus imaging, optomotor testing, and photoreceptor-specific gene expression. Together, these findings provide independent in vivo evidence for the neuroprotective effect of LP-CN03 in both cGMP-related RP and LCA, also highlighting the translational value of kinome profiling.
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BibTeX
@misc{okan2026identification,
title = {{Identification of Kinome Biomarkers and Therapeutic Rescue in cGMP-Linked Retinal Degeneration}},
author = {I. C. Topcu Okan and M. Ahmadian and H. Y. Altay and S. Pal Singh and G. Kheirandish and S. Ozer and P. Gaillard and R. Bouffard and A. Neutzner and K. Esmen and M. Tschopp and M. Lawrence and M. K. Diril and F. Paquet-Durand and C. Agca},
howpublished = {bioRxiv},
year = {2026},
month = nov,
doi = {10.64898/2026.11.06.763903},
url = {https://www.biorxiv.org/content/10.64898/2026.11.06.763903v1},
note = {CC BY-NC},
}
RIS
TY - UNPB
TI - Identification of Kinome Biomarkers and Therapeutic Rescue in cGMP-Linked Retinal Degeneration
AU - I. C. Topcu Okan
AU - M. Ahmadian
AU - H. Y. Altay
AU - S. Pal Singh
AU - G. Kheirandish
AU - S. Ozer
AU - P. Gaillard
AU - R. Bouffard
AU - A. Neutzner
AU - K. Esmen
AU - M. Tschopp
AU - M. Lawrence
AU - M. K. Diril
AU - F. Paquet-Durand
AU - C. Agca
PY - 2026
DA - 2026/11/06
PB - bioRxiv
DO - 10.64898/2026.11.06.763903
UR - https://www.biorxiv.org/content/10.64898/2026.11.06.763903v1
AB - Inherited retinal degenerations, such as Retinitis Pigmentosa (RP) and Leber's congenital amaurosis (LCA), are major causes of progressive and irreversible vision loss. The large number of genes associated with these disorders makes their clinical and molecular characterization difficult, while systemic biomarkers for disease progression or treatment response remain limited. These challenges were addressed by targeting cGMP-associated mechanisms shared by RP and LCA and integrating systemic biomarker profiling with retinal outcomes. Kinase activity analysis (kinome analysis) in peripheral blood mononuclear cells distinguished healthy and diseased states and captured therapy-associated signatures in rd10 mice treated with LP-CN03, a liposomal formulation of the cGMP analog CN03. This first systemic analysis in a therapeutically responsive animal model highlights kinome analysis as a potential translational readout. Given shared cGMP signaling in RP and AIPL1-associated LCA, LP-CN03's therapeutic potential was further evaluated in a new CRISPR-Cas9-generated Aipl1-/- mouse model. Treatment with LP-CN03 preserved retinal structure and function, as shown by electroretinography, longitudinal optical coherence tomography, fundus imaging, optomotor testing, and photoreceptor-specific gene expression. Together, these findings provide independent in vivo evidence for the neuroprotective effect of LP-CN03 in both cGMP-related RP and LCA, also highlighting the translational value of kinome profiling.
ER -