Biology subjects

Sbornova, I.

Publications and source records attributed to Sbornova, I..

2 recordsLinked to original sources

bioRxiv2026

Age-Related Upregulation and Strong Expression Correlation of the Proinflammatory Cytokines IL-1β and IL-6 Across Multiple Segments of the Mouse Eye

Emerging evidence suggests that ocular inflammation increases with age and is associated with various disease states. That said, the majority of studies suffer from a significant limitation--they only focus on a single segment of the eye. This represents a limitation because age-related increases in neuroinflammatory markers are not necessarily uniform within an organ, and other age-related changes in the eye are known to occur in a segment-specific manner. The present study aims to address this gap by comparting/contrasting age-related changes in the proinflammatory cytokines IL-6 and IL-1{beta} across multiple mouse ocular segments: the (i) anterior segment (i.e., cornea, ciliary body and muscle, and zonules), (ii) retina, and (iii) posterior segment (i.e., sclera, choroid, Bruchs membrane, retinal pigmented epithelium, and parts of the optic nerve). IL-6 and IL-1{beta} were selected as targets since they exhibit differential regional patterns of age-related increases within the brain. Eyes were collected on postnatal days (P) P28, P56, P98, P200 and P500 and processed by Western blot. Both IL-6 and IL-1{beta} protein levels increased across the lifespan in all three eye segments. Interestingly, correlational analyses revealed that IL-1{beta} and IL-6 expression correlated with each other not only within individual eye segments, but also across segments. In old mice, IL-1{beta} and IL-6 levels also correlated with expression of phosphodiesterase 11A (PDE11A), an enzyme known to regulate neuroinflammation. Together, these findings suggest that inflammaging in the eye is broadly controlled by a systemic governor, unlike the brain that shows region-specific changes in cytokines with age.

neuroscience↗

bioRxiv2023

The sleep quality- and myopia-linked PDE11A-Y727C variant impacts neural physiology by reducing catalytic activity and altering subcellular compartmentalization of the enzyme

Recently, a Y727C variant in the dual-specific 3,5-cyclic nucleotide phosphodiesterase 11A (PDE11A-Y727C) was linked to increased sleep quality and reduced myopia risk in humans. Given the well-established role that the PDE11 substrates cAMP and cGMP play in eye physiology and sleep, we determined if 1) PDE11A protein is expressed in the retina or other eye segments in mouse, 2) PDE11A-Y7272C affects catalytic activity and/or subcellular compartmentalization more so than the nearby suicide-associated PDE11A-M878V variant, and 3) Pde11a deletion alters eye growth or sleep quality in male and female mice. Western blots show distinct protein expression of PDE11A4, but not PDE11A1-3, in eyes of Pde11a WT--but not KO mice--that vary by eye segment and age. In HT22 and COS-1 cells, PDE11A4-Y727C reduces PDE11A4 catalytic activity far more than PDE11A4-M878V, with both variants reducing PDE11A4-cAMP more so than PDE11A4-cGMP activity. Despite this, Pde11a deletion does not alter age-related changes in retinal or lens thickness, axial length, nor vitreous or anterior chamber depth. Further, Pde11a deletion only minimally changes refractive error and sleep quality. That said, both variants also dramatically alter the subcellular compartmentalization of human and mouse PDE11A4, an effect occurring independently of dephosphorylating PDE11A4-S117/S124 or phosphorylating PDE11A4-S162. Rather, re-compartmentalization of PDE11A4-Y727C is due to the loss of the tyrosine changing how PDE11A4 is packaged/repackaged via the trans-Golgi network. Therefore, the protective impact of the Y727C variant may reflect a gain-of-function (e.g., PDE11A4 displacing another PDE) that warrants further investigation in the context of reversing/preventing sleep disturbances or myopia.

neuroscience↗