Impact of keratocyte differentiation on corneal opacity resolution and visual function recovery in male rats.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
11 Jun 2024
11 Jun 2024
Historique:
received:
23
06
2023
accepted:
17
05
2024
medline:
12
6
2024
pubmed:
12
6
2024
entrez:
11
6
2024
Statut:
epublish
Résumé
Intrastromal cell therapy utilizing quiescent corneal stromal keratocytes (qCSKs) from human donor corneas emerges as a promising treatment for corneal opacities, aiming to overcome limitations of traditional surgeries by reducing procedural complexity and donor dependency. This investigation demonstrates the therapeutic efficacy of qCSKs in a male rat model of corneal stromal opacity, underscoring the significance of cell-delivery quality and keratocyte differentiation in mediating corneal opacity resolution and visual function recovery. Quiescent CSKs-treated rats display improvements in escape latency and efficiency compared to wounded, non-treated rats in a Morris water maze, demonstrating improved visual acuity, while stromal fibroblasts-treated rats do not. Advanced imaging, including multiphoton microscopy, small-angle X-ray scattering, and transmission electron microscopy, revealed that qCSK therapy replicates the native cornea's collagen fibril morphometry, matrix order, and ultrastructural architecture. These findings, supported by the expression of keratan sulfate proteoglycans, validate qCSKs as a potential therapeutic solution for corneal opacities.
Identifiants
pubmed: 38862465
doi: 10.1038/s41467-024-49008-3
pii: 10.1038/s41467-024-49008-3
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
4959Subventions
Organisme : MOH | National Medical Research Council (NMRC)
ID : MOH-000197-00
Informations de copyright
© 2024. The Author(s).
Références
Jinabhai, A., O’Donnell, C., Radhakrishnan, H. & Nourrit, V. Forward light scatter and contrast sensitivity in keratoconic patients. Cont. Lens Anterior Eye 35, 22–27 (2012).
pubmed: 21813314
doi: 10.1016/j.clae.2011.07.001
Wang, E. Y. et al. Global trends in blindness and vision impairment resulting from corneal opacity 1984-2020: a meta-analysis. Ophthalmology 130, 863–871 (2023).
pubmed: 36963570
doi: 10.1016/j.ophtha.2023.03.012
Yam, G. H. F., Riau, A. K., Funderburgh, M. L., Mehta, J. S. & Jhanji, V. Keratocyte biology. Exp. Eye Res. 196, 108062 (2020).
pubmed: 32442558
doi: 10.1016/j.exer.2020.108062
Jester, J. V. et al. The cellular basis of corneal transparency: evidence for ‘corneal crystallins’. J. Cell Sci. 112, 613–622 (1999).
pubmed: 9973596
doi: 10.1242/jcs.112.5.613
Kao, W. W. Y. & Liu, C.-Y. Roles of lumican and keratocan on corneal transparency. Glycoconj. J. 19, 275–285 (2002).
pubmed: 12975606
doi: 10.1023/A:1025396316169
Hassell, J. R. & Birk, D. E. The molecular basis of corneal transparency. Exp. Eye Res. 91, 326–335 (2010).
pubmed: 20599432
pmcid: 3726544
doi: 10.1016/j.exer.2010.06.021
Jester, J. V. et al. Evaluating corneal collagen organization using high-resolution nonlinear optical macroscopy. Eye Contact Lens 36, 260–264 (2010).
pubmed: 20724856
pmcid: 2945240
doi: 10.1097/ICL.0b013e3181ee8992
Wilson, S. E., Sampaio, L. P., Shiju, T. M., Hilgert, G. S. L. & de Oliveira, R. C. Corneal opacity: cell biological determinants of the transition from transparency to transient haze to scarring fibrosis, and resolution, after injury. Invest. Ophthalmol. Vis. Sci. 63, 22 (2022).
pubmed: 35044454
pmcid: 8787546
doi: 10.1167/iovs.63.1.22
Mohan, R. R., Kempuraj, D., D’Souza, S. & Ghosh, A. Corneal stromal repair and regeneration. Prog. Retin. Eye Res. 91, 101090 (2022).
pubmed: 35649962
doi: 10.1016/j.preteyeres.2022.101090
Kamil, S. & Mohan, R. R. Corneal stromal wound healing: major regulators and therapeutic targets. Ocul. Surf. 19, 290–306 (2021).
pubmed: 33127599
doi: 10.1016/j.jtos.2020.10.006
Fukuda, K. Corneal fibroblasts: function and markers. Exp. Eye Res. 200, 108229 (2020).
pubmed: 32919991
doi: 10.1016/j.exer.2020.108229
Jester, J. V., Brown, D., Pappa, A. & Vasiliou, V. Myofibroblast differentiation modulates keratocyte crystallin protein expression, concentration, and cellular light scattering. Invest. Ophthalmol. Vis. Sci. 53, 770–778 (2012).
pubmed: 22247459
pmcid: 3317419
doi: 10.1167/iovs.11-9092
Sher, N. A. et al. Clinical use of the 193-nm excimer laser in the treatment of corneal scar. Arch. Ophthalmol. 109, 491–498 (1991).
pubmed: 2012547
doi: 10.1001/archopht.1991.01080040059027
Homer, D. G., Soni, P. S., Heath, G. G. & Gerstman, D. R. Management of scarred cornea with RGP contact lens. Int. Contact Lens Clin. 18, 9–13 (1991).
doi: 10.1016/0892-8967(91)90037-Z
Tan, D. T. H., Dart, J. K. G., Holland, E. J. & Kinoshita, S. Corneal transplantation. Lancet 379, 1749–1761 (2012).
pubmed: 22559901
doi: 10.1016/S0140-6736(12)60437-1
Wong, K. H., Kam, K. W., Chen, L. J. & Young, A. L. Corneal blindness and current major treatment concern-graft scarcity. Int. J. Ophthalmol. 10, 1154–1162 (2017).
pubmed: 28730122
pmcid: 5514281
Panda, A., Vanathi, M., Kumar, A., Dash, Y. & Priya, S. Corneal graft rejection. Surv. Ophthalmol. 52, 375–396 (2007).
pubmed: 17574064
doi: 10.1016/j.survophthal.2007.04.008
Lam, H. & Dana, M. R. Corneal graft rejection. Int. Ophthalmol. Clin. 49, 31–41 (2009).
pubmed: 19125062
doi: 10.1097/IIO.0b013e3181924e23
Pinnamaneni, N. & Funderburgh, J. L. Concise review: stem cells in the corneal stroma. Stem Cells 30, 1059–1063 (2012).
pubmed: 22489057
doi: 10.1002/stem.1100
Alió Del Barrio, J. L. et al. Corneal regeneration using adipose-derived mesenchymal stem cells. Cells 11, 2549 (2022).
pubmed: 36010626
pmcid: 9406486
doi: 10.3390/cells11162549
Yam, G. H.-F. et al. Ex vivo propagation of human corneal stromal “activated keratocytes” for tissue engineering. Cell Transplant. 24, 1845–1861 (2015).
pubmed: 25291523
doi: 10.3727/096368914X685069
Yam, G. H.-F. et al. Safety and feasibility of intrastromal injection of cultivated human corneal stromal keratocytes as cell-based therapy for corneal opacities. Invest. Ophthalmol. Vis. Sci. 59, 3340–3354 (2018).
pubmed: 30025076
doi: 10.1167/iovs.17-23575
Funderburgh, J. L. Keratan sulfate biosynthesis. IUBMB Life 54, 187–194 (2002).
pubmed: 12512857
pmcid: 2874674
doi: 10.1080/15216540214932
Du, Y., Funderburgh, M. L., Mann, M. M., SundarRaj, N. & Funderburgh, J. L. Multipotent stem cells in human corneal stroma. Stem Cells 23, 1266–1275 (2005).
pubmed: 16051989
doi: 10.1634/stemcells.2004-0256
Pei, Y., Sherry, D. M. & McDermott, A. M. Thy-1 distinguishes human corneal fibroblasts and myofibroblasts from keratocytes. Exp. Eye Res. 79, 705–712 (2004).
pubmed: 15500828
doi: 10.1016/j.exer.2004.08.002
Jester, J. V., Petroll, W. M., Barry, P. A. & Cavanagh, H. D. Expression of alpha-smooth muscle (alpha-SM) actin during corneal stromal wound healing. Invest. Ophthalmol. Vis. Sci. 36, 809–819 (1995).
pubmed: 7706029
Tuori, A., Virtanen, I., Aine, E. & Uusitalo, H. The expression of tenascin and fibronectin in keratoconus, scarred and normal human cornea. Graefes Arch. Clin. Exp. Ophthalmol. 235, 222–229 (1997).
pubmed: 9143890
doi: 10.1007/BF00941763
Karamichos, D., Guo, X. Q., Hutcheon, A. E. K. & Zieske, J. D. Human corneal fibrosis: an in vitro model. Invest. Ophthalmol. Vis. Sci. 51, 1382–1388 (2010).
pubmed: 19875671
pmcid: 2868432
doi: 10.1167/iovs.09-3860
Boote, C. et al. Quantitative assessment of ultrastructure and light scatter in mouse corneal debridement wounds. Invest. Ophthalmol. Vis. Sci. 53, 2786–2795 (2012).
pubmed: 22467580
pmcid: 3367468
doi: 10.1167/iovs.11-9305
Bhuiyan, S. et al. Assessment of renal fibrosis and anti-fibrotic agents using a novel diagnostic and stain-free second-harmonic generation platform. FASEB J. 35, e21595 (2021).
pubmed: 33908676
doi: 10.1096/fj.202002053RRR
Shojaati, G. et al. Compressed collagen enhances stem cell therapy for corneal scarring. Stem Cells Transl. Med. 7, 487–494 (2018).
pubmed: 29654654
pmcid: 5980128
doi: 10.1002/sctm.17-0258
Zhou, Y., Chen, Y., Wang, S., Qin, F. & Wang, L. MSCs helped reduce scarring in the cornea after fungal infection when combined with anti-fungal treatment. BMC Ophthalmol. 19, 226 (2019).
pubmed: 31727008
pmcid: 6857224
doi: 10.1186/s12886-019-1235-6
Lindner, M. D. & Gribkoff, V. K. Relationship between performance in the Morris water task, visual acuity, and thermoregulatory function in aged F-344 rats. Behav. Brain Res. 45, 45–55 (1991).
pubmed: 1764204
doi: 10.1016/S0166-4328(05)80179-2
Guo, X. et al. Morphologic characterization of organized extracellular matrix deposition by ascorbic acid-stimulated human corneal fibroblasts. Invest. Ophthalmol. Vis. Sci. 48, 4050–4060 (2007).
pubmed: 17724187
doi: 10.1167/iovs.06-1216
Andresen, J. L., Ledet, T. & Ehlers, N. Keratocyte migration and peptide growth factors: the effect of PDGF, bFGF, EGF, IGF-I, aFGF and TGF-beta on human keratocyte migration in a collagen gel. Curr. Eye Res. 16, 605–613 (1997).
pubmed: 9192171
doi: 10.1076/ceyr.16.6.605.5081
Wilson, S. E. Corneal myofibroblasts and fibrosis. Exp. Eye Res. 201, 108272 (2020).
pubmed: 33010289
pmcid: 7736212
doi: 10.1016/j.exer.2020.108272
Gupta, R. et al. Mitomycin C: a promising agent for the treatment of canine corneal scarring. Vet. Ophthalmol. 14, 304–312 (2011).
pubmed: 21929607
pmcid: 3354612
doi: 10.1111/j.1463-5224.2011.00877.x
Grupcheva, C. N. et al. Improved corneal wound healing through modulation of gap junction communication using connexin43-specific antisense oligodeoxynucleotides. Invest. Ophthalmol. Vis. Sci. 53, 1130–1138 (2012).
pubmed: 22247467
doi: 10.1167/iovs.11-8711
Torricelli, A. A. & Wilson, S. E. Cellular and extracellular matrix modulation of corneal stromal opacity. Exp. Eye Res. 129, 151–160 (2014).
pubmed: 25281830
doi: 10.1016/j.exer.2014.09.013
Leonardi, A. et al. Cytokine and chemokine levels in tears and in corneal fibroblast cultures before and after excimer laser treatment. J. Cataract Refract. Surg. 35, 240–247 (2009).
pubmed: 19185237
doi: 10.1016/j.jcrs.2008.10.030
Jhanji, V. et al. Combined therapy using human corneal stromal stem cells and quiescent keratocytes to prevent corneal scarring after injury. Int. J. Mol. Sci. 23, 6980 (2022).
pubmed: 35805991
pmcid: 9267074
doi: 10.3390/ijms23136980
Rafat, M. et al. Bioengineered corneal tissue for minimally invasive vision restoration in advanced keratoconus in two clinical cohorts. Nat. Biotechnol. 41, 70–81 (2023).
pubmed: 35953672
doi: 10.1038/s41587-022-01408-w
Chen, F. et al. In situ-forming collagen-hyaluronate semi-interpenetrating network hydrogel enhances corneal defect repair. Transl. Vis. Sci. Technol. 11, 22 (2022).
pubmed: 36239965
pmcid: 9586141
doi: 10.1167/tvst.11.10.22
Sayan, B. et al. Human limbal biopsy–derived stromal stem cells prevent corneal scarring. Sci. Transl. Med. 6, 266ra172 (2014).
Funderburgh, J. et al. Limbal stromal stem cell therapy for acute and chronic superficial corneal pathologies: one-year outcomes. Invest. Ophthalmol. Vis. Sci. 59, 3455–3455 (2018).
Branch, M. J. et al. Mesenchymal stem cells in the human corneal limbal stroma. Invest. Ophthalmol. Vis. Sci. 53, 5109–5116 (2012).
pubmed: 22736610
doi: 10.1167/iovs.11-8673
Weng, L. et al. The anti-scarring effect of corneal stromal stem cell therapy is mediated by transforming growth factor β3. Eye Vis. 7, 52 (2020).
doi: 10.1186/s40662-020-00217-z
Shojaati, G. et al. Mesenchymal stem cells reduce corneal fibrosis and inflammation via extracellular vesicle-mediated delivery of miRNA. Stem Cells Transl. Med. 8, 1192–1201 (2019).
pubmed: 31290598
pmcid: 6811691
doi: 10.1002/sctm.18-0297
Tan, T. E. et al. A cost-minimization analysis of tissue-engineered constructs for corneal endothelial transplantation. PLoS ONE 9, e100563 (2014).
pubmed: 24949869
pmcid: 4065108
doi: 10.1371/journal.pone.0100563
Arnalich-Montiel, F. et al. Adipose-derived stem cells are a source for cell therapy of the corneal stroma. Stem Cells 26, 570–579 (2008).
pubmed: 18065394
doi: 10.1634/stemcells.2007-0653
Prusky, G. T., West, P. W. & Douglas, R. M. Behavioral assessment of visual acuity in mice and rats. Vision Res. 40, 2201–2209 (2000).
pubmed: 10878281
doi: 10.1016/S0042-6989(00)00081-X
Yusoff, N. Z. B. M., Riau, A. K., Yam, G. H. F., Halim, N. S. H. B. & Mehta, J. S. Isolation and propagation of human corneal stromal keratocytes for tissue engineering and cell therapy. Cells 11, 178 (2022).
doi: 10.3390/cells11010178
Chaurasia, S. S. et al. Hevin plays a pivotal role in corneal wound healing. PLoS ONE 8, e81544 (2013).
pubmed: 24303054
pmcid: 3841198
doi: 10.1371/journal.pone.0081544
LeBlanc, M. E. et al. Hepatoma-derived growth factor-related protein-3 is a novel angiogenic factor. PLoS ONE 10, e0127904 (2015).
pubmed: 25996149
pmcid: 4440747
doi: 10.1371/journal.pone.0127904
Fantes, F. E. et al. Wound healing after excimer laser keratomileusis (photorefractive keratectomy) in monkeys. Arch. Ophthalmol. 108, 665–675 (1990).
pubmed: 2334323
doi: 10.1001/archopht.1990.01070070051034
Young, R. D. et al. Stromal edema in Klf4 conditional null mouse cornea is associated with altered collagen fibril organization and reduced proteoglycans. Invest. Ophthalmol. Vis. Sci. 50, 4155–4161 (2009).
pubmed: 19387067
doi: 10.1167/iovs.09-3561
Abass, A. et al. SAXS4COLL: an integrated software tool for analysing fibrous collagen-based tissues. J. Appl. Crystallogr. 50, 1235–1240 (2017).
pubmed: 28808439
pmcid: 5541358
doi: 10.1107/S1600576717007877
Nunez, J. Morris water maze experiment. J. Vis. Exp. 19, 897 (2008).