Corneal Stromal Regeneration: Current Status and Future Therapeutic Potential

[PhilLer]

Corneal Stromal Regeneration: Current Status and Future Therapeutic Potential
Neil Lagali 1 2
Affiliations expand
PMID: 31537127 DOI: 10.1080/02713683.2019.1663874
Free article
Abstract
The corneal stroma comprises 90% of the corneal thickness and is critical for the cornea's transparency and refractive function necessary for vision. When the corneal stroma is altered by disease, injury, or scarring, however, an irreversible loss of transparency can occur. Corneal stromal pathology is the cause of millions of cases of blindness globally, and although corneal transplantation is the standard therapy, a severe global deficit of donor corneal tissue and eye banking infrastructure exists, and is unable to meet the overwhelming need. An alternative approach is to harness the endogenous regenerative ability of the corneal stroma, which exhibits self-renewal of the collagenous extracellular matrix under appropriate conditions. To mimic endogenous stromal regeneration, however, is a challenge. Unlike the corneal epithelium and endothelium, the corneal stroma is an exquisitely organized extracellular matrix containing stromal cells, proteoglycans and corneal nerves that is difficult to recapitulate in vitro. Nevertheless, much progress has recently been made in developing stromal equivalents, and in this review the most recent approaches to stromal regeneration therapy are described and discussed. Novel approaches for stromal regeneration include human or animal corneal and/or non-corneal tissue that is acellular or is decellularized and/or re-cellularized, acellular bioengineered stromal scaffolds, tissue adhesives, 3D bioprinting and stromal stem cell therapy. This review highlights the techniques and advances that have achieved first clinical use or are close to translation for eventual therapeutic application in repairing and regenerating the corneal stroma, while the potential of these novel therapies for achieving effective stromal regeneration is discussed.

Keywords: 3D bioprinting; Corneal stroma; acellular porcine cornea; bioengineered cornea; stromal regeneration; stromal stem cells.

Curr Eye Res. 2020 Mar;45(3):278-290. doi: 10.1080/02713683.2019.1663874. Epub 2019 Sep 20.
https://pubmed.ncbi.nlm.nih.gov/31537127/

[PhilLer]

Another very interesting papers about keratoconus and corneal stroma

Exp Eye Res
. 1999 Nov;69(5):475-81. doi: 10.1006/exer.1999.0719.
Keratocyte apoptosis associated with keratoconus
W J Kim 1, Y S Rabinowitz, D M Meisler, S E Wilson
Affiliations expand
PMID: 10548467 DOI: 10.1006/exer.1999.0719
Abstract
Keratoconus is an ectatic corneal dystrophy associated with stromal thinning and disruption of Bowman's layer. The purpose of this study was to explore a possible association between keratocyte apoptosis and keratoconus. Keratocyte apoptosis was evaluated in corneas of patients with keratoconus, corneas of patients with stromal dystrophies, and normal donor corneas using the transferase-mediated dUTP-digoxigenin nick and labeling (TUNEL) assay. Keratocyte apoptosis was also studied in keratoconus and normal corneas using transmission electron microscopy. TUNEL-stained keratocytes were detected in 60% of corneas with keratoconus, but only 35% of corneas with stromal dystrophies (P =0.03). The number of TUNEL-positive keratocytes detected in the keratoconus, stromal dystrophy, and normal corneas was 7+/-1 (mean+/-standard error, range 0-20), 2+/-0. 8 (range 0-9), and 0+/-0 (range 0-0) TUNEL-positive cells per section, respectively. The differences between the keratoconus and the stromal dystrophy (P =0.0097) or the normal cornea (P =0.01) groups were statistically significant. The difference between the stromal dystrophy and normal cornea groups was not statistically significant (P =0.45). The stromal dystrophy group was included to account for surgery-associated keratocyte apoptosis. No TUNEL-stained keratocytes were detected in normal corneas. Cell morphologic changes consistent with apoptosis were detected by transmission electron microscopy (TEM) in keratocytes of keratoconus corneas, but not in keratocytes in normal corneas. Chronic keratocyte apoptosis associated with ongoing epithelial injury may link risk factors associated with keratoconus such as chronic eye rubbing, contact lens wear, or atopic eye disease. Similarly, increases that have been detected in several different degradative enzymes in keratoconus corneas could be associated with chronic keratocyte apoptosis and less than perfect control of release of intracellular contents.

https://pubmed.ncbi.nlm.nih.gov/1054846 ... %20disease.


Elsevier
Acta Biomaterialia
Volume 69, 15 March 2018, Pages 31-41
Acta Biomaterialia
Review article
Corneal regeneration: A review of stromal replacements
Author links open overlay panelSteffiMatthyssenaBertVan den BogerdaSorcha NíDhubhghaillabCarinaKoppenabNadiaZakariaabc
Under a Creative Commons licenseopen access
Abstract
Corneal blindness is traditionally treated by transplantation of a donor cornea, or in severe cases by implantation of an artificial cornea or keratoprosthesis. Due to severe donor shortages and the risks of complications that come with artificial corneas, tissue engineering in ophthalmology has become more focused on regenerative strategies using biocompatible materials either with or without cells. The stroma makes up the bulk of the corneal thickness and mainly consists of a tightly interwoven network of collagen type I, making it notoriously difficult to recreate in a laboratory setting. Despite the challenges that come with corneal stromal tissue engineering, there has recently been enormous progress in this field. A large number of research groups are working towards developing the ideal biomimetic, cytocompatible and transplantable stromal replacement. Here we provide an overview of the approaches directed towards tissue engineering the corneal stroma, from classical collagen gels, films and sponges to less traditional components such as silk, fish scales, gelatin and polymers. The perfect stromal replacement has yet to be identified and future research should be directed at combined approaches, in order to not only host native stromal cells but also restore functionality.

Statement of Significance
In the field of tissue engineering and regenerative medicine in ophthalmology the focus has shifted towards a common goal: to restore the corneal stroma and thereby provide a new treatment option for patients who are currently blind due to corneal opacification. Currently the waiting lists for corneal transplantation include more than 10 million patients, due to severe donor shortages. Alternatives to the transplantation of a donor cornea include the use of artificial cornea, but these are by no means biomimetic and therefore do not provide good outcomes. In recent years a lot of work has gone into the development of tissue engineered scaffolds and other biomaterials suitable to replace the native stromal tissue. Looking at all the different approaches separately is a daunting task and up until now there was no review article in which every approach is discussed. This review does include all approaches, from classical tissue engineering with collagen to the use of various alternative biomaterials and even fish scales. Therefore, this review can serve as a reference work for those starting in the field and but also to stimulate collaborative efforts in the future.

https://www.sciencedirect.com/science/a ... 6118300345

Philippe