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Purpose of Review <p>Cataracts are the leading cause of blindness worldwide. Standard treatment, lentectomy with intraocular lens implantation, restores visual acuity but eliminates accommodation and carries risk of posterior capsular opacification. Regenerating a functional, autologous crystalline lens would afford patients preserved accommodation and reduce long-term complications. This review integrates lens anatomy and embryology, comparative regeneration models, single-cell atlases, stem-cell differentiation advances, emerging biomaterial and bioprinting strategies, and recent progress in minimally invasive capsule-preserving pediatric surgery to outline the current trajectory toward clinically viable lens regeneration.</p> Recent Findings <p>Single-cell RNA sequencing has revealed a hierarchical differentiation organization of several sub-populations in the human lens epithelium with a stem/progenitor-like cluster at the apex of a differentiation cascade. Transcriptomic analysis also indicates that aging downregulates adhesion-junction expression and upregulates mitochondrial pathways, contributing to cataract pathology. Transparent hydrogel and 3D-bioprinted scaffolds now support stem cell encapsulation and differentiation and lens epithelial cell survival and can achieve high optical transmission. In infants, minimally invasive lens-content removal surgery yields functional lens regeneration, and metabolic adjuncts including nicotinamide are being evaluated for use in improving clarity and accelerating regeneration.</p> Summary <p>Lens regeneration research has progressed from descriptive amphibian models to a mechanistic, single-cell resolution understanding with early clinical translation. A defined epithelial differentiation hierarchy, retained progenitor reservoir, reproducible capsule-preserving surgical techniques, and improving biomimetic scaffolds create a feasible pathway toward adult human lens regeneration. Key priorities for future work include reactivating dormant progenitor cell populations in adult capsules, optimizing scaffold architecture and physicochemical properties to suppress opacification, modulating FGF/BMP/Wnt signaling, and elucidating the role of resident immune cells. Addressing these priorities will be pivotal for advancing lens regeneration into a therapeutic reality.</p>

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Crystalline Lens Regeneration: A Review

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年1月19日

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  • Adam Nelson,
  • Caitlin Logan,
  • Alyssa Manche,
  • David Myung

摘要

Purpose of Review

Cataracts are the leading cause of blindness worldwide. Standard treatment, lentectomy with intraocular lens implantation, restores visual acuity but eliminates accommodation and carries risk of posterior capsular opacification. Regenerating a functional, autologous crystalline lens would afford patients preserved accommodation and reduce long-term complications. This review integrates lens anatomy and embryology, comparative regeneration models, single-cell atlases, stem-cell differentiation advances, emerging biomaterial and bioprinting strategies, and recent progress in minimally invasive capsule-preserving pediatric surgery to outline the current trajectory toward clinically viable lens regeneration.

Recent Findings

Single-cell RNA sequencing has revealed a hierarchical differentiation organization of several sub-populations in the human lens epithelium with a stem/progenitor-like cluster at the apex of a differentiation cascade. Transcriptomic analysis also indicates that aging downregulates adhesion-junction expression and upregulates mitochondrial pathways, contributing to cataract pathology. Transparent hydrogel and 3D-bioprinted scaffolds now support stem cell encapsulation and differentiation and lens epithelial cell survival and can achieve high optical transmission. In infants, minimally invasive lens-content removal surgery yields functional lens regeneration, and metabolic adjuncts including nicotinamide are being evaluated for use in improving clarity and accelerating regeneration.

Summary

Lens regeneration research has progressed from descriptive amphibian models to a mechanistic, single-cell resolution understanding with early clinical translation. A defined epithelial differentiation hierarchy, retained progenitor reservoir, reproducible capsule-preserving surgical techniques, and improving biomimetic scaffolds create a feasible pathway toward adult human lens regeneration. Key priorities for future work include reactivating dormant progenitor cell populations in adult capsules, optimizing scaffold architecture and physicochemical properties to suppress opacification, modulating FGF/BMP/Wnt signaling, and elucidating the role of resident immune cells. Addressing these priorities will be pivotal for advancing lens regeneration into a therapeutic reality.