A comprehensive atlas of Aggrecan, Versican, Neurocan and Phosphacan expression across time in wildtype retina and in retinal degeneration

Scientific Reports, 2022 · DOI: 10.1038/s41598-022-11204-w · Published: April 7, 2022

Simple Explanation

This study examines how the expression patterns of four specific Chondroitin Sulphate Proteoglycans (CSPGs) change in the retinas of mice with inherited retinal degeneration, compared to normal mice. CSPGs are important components of the extracellular matrix and can affect neuronal growth and regeneration. The researchers looked at Aggrecan, Versican, Neurocan, and Phosphacan in three different mouse models of retinal degeneration, as well as in wildtype mice, across different stages of retinal development and degeneration. The findings reveal that the expression of these CSPGs varies significantly during retinal degeneration, with some increasing and others decreasing, and that these changes differ between different models of the disease. This suggests that the microenvironment of the retina changes in complex ways during degeneration.

Study Duration

Not specified

Participants

Wildtype C57BL/6 J mice, Rho-/-, Aipl1-/-, and Pde6brd1/rd1 mice

Evidence Level

Not specified

Key Findings

1
In wildtype mice, Aggrecan showed a biphasic expression pattern, Neurocan and Phosphacan expression decreased with time, while Versican expression remained broadly constant.
2
In models of retinal degeneration, Aggrecan expression increased markedly in Aipl1-/- and Pde6brd1/rd1 mice, while Versican showed regional increases in the periphery of Rho-/- mice.
3
Neurocan and Phosphacan generally decreased with time in all models of retinal degeneration.

Research Summary

This study comprehensively maps the expression patterns of four individual CSPGs (Aggrecan, Versican, Neurocan, and Phosphacan) in wildtype mice and in three murine models of inherited retinal degeneration across different time points. The research reveals significant heterogeneity in the expression of individual CSPGs, both in the normal retina and during degeneration, highlighting the importance of understanding the specific microenvironment changes associated with a given disease type when assessing therapeutic interventions. The findings provide a valuable resource and reference for future studies aimed at creating more permissive microenvironments for neuro-regeneration and repair in the retina.

Practical Implications

Therapeutic Targeting of CSPGs

Understanding the distinct distributions of individual CSPGs can help in creating more permissive microenvironments for neuro-regeneration and repair in the retina.

Personalized Therapeutic Strategies

The heterogeneity in CSPG expression between different retinal degeneration models suggests the need for personalized therapeutic strategies tailored to specific disease types.

Optimizing Timing of Interventions

The changes in CSPG expression across different stages of degeneration highlight the importance of considering the timing of therapeutic interventions to maximize their efficacy.

Study Limitations

1
The study is limited to murine models of retinal degeneration, and the findings may not directly translate to human disease.
2
The study focuses on only four CSPGs, and other CSPGs may also play a significant role in retinal degeneration.
3
The study did not investigate the functional consequences of the observed changes in CSPG expression.

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