Myo/Nog Cells: The Jekylls and Hydes of the Lens

by Selleckchem | Dec 26 2023

Herein, we review a unique and versatile lineage composed of Myo/Nog cells that may be beneficial or detrimental depending on their environment and nature of the pathological stimuli they are exposed to. While we will focus on the lens, related Myo/Nog cell behaviors and functions in other tissues are integrated into the narrative of our research that spans over three decades, examines multiple species and progresses from early stages of embryonic development to aging adults. Myo/Nog cells were discovered in the embryonic epiblast by their co-expression of the skeletal muscle-specific transcription factor MyoD, the bone morphogenetic protein inhibitor Noggin and brain-specific angiogenesis inhibitor 1. They were tracked from the epiblast into the developing lens, revealing heterogeneity of cell types within this structure. Depletion of Myo/Nog cells in the epiblast results in eye malformations arising from the absence of Noggin. In the adult lens, Myo/Nog cells are the source of myofibroblasts whose contractions produce wrinkles in the capsule. Eliminating this population within the rabbit lens during cataract surgery reduces posterior capsule opacification to below clinically significant levels. Parallels are drawn between the therapeutic potential of targeting Myo/Nog cells to prevent fibrotic disease in the lens and other ocular tissues.

Comments:

This is a fascinating study that delves into the multifaceted behavior of Myo/Nog cells and their implications in various developmental and pathological contexts. The lineage's versatility, as you've described, showcases both its potential benefits and detriments contingent on its microenvironment and the stimuli encountered.

The discovery of Myo/Nog cells in the embryonic epiblast, identified by their co-expression of MyoD, Noggin, and brain-specific angiogenesis inhibitor 1, presents an intriguing starting point. Their migration into the developing lens, revealing diverse cell types within this structure, suggests their involvement in the complex architecture and functionality of the lens itself.

The link between the depletion of Myo/Nog cells in the epiblast and subsequent eye malformations due to the absence of Noggin underscores the critical role played by this lineage in proper eye development. This finding likely emphasizes their regulatory function in maintaining the balance of signaling pathways crucial for normal organogenesis.

Moreover, the identification of Myo/Nog cells as the source of myofibroblasts in the adult lens, contributing to capsule wrinkling, indicates their involvement in tissue remodeling processes. The implication that eliminating this population during cataract surgery can significantly reduce posterior capsule opacification is particularly intriguing from a clinical standpoint, hinting at potential therapeutic interventions targeting Myo/Nog cells to mitigate fibrotic diseases not only in the lens but also in other ocular tissues.

The integration of findings from multiple species and across various developmental stages and aging adults offers a comprehensive perspective on the behavior and functions of Myo/Nog cells, potentially paving the way for novel therapeutic strategies in ocular pathology. The parallels drawn between the lens and other ocular tissues in terms of therapeutic targeting highlight the broader implications and translational potential of this research.

Overall, your review underscores the intricate nature of Myo/Nog cells and their dynamic roles in development, tissue maintenance, and pathology, laying the groundwork for potential therapeutic interventions in ocular disorders.