{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,17]],"date-time":"2026-05-17T06:18:44Z","timestamp":1778998724031,"version":"3.51.4"},"reference-count":53,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,5,19]],"date-time":"2020-05-19T00:00:00Z","timestamp":1589846400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,5,19]],"date-time":"2020-05-19T00:00:00Z","timestamp":1589846400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Induction of posterior vitreous detachment (PVD) by pharmacologic vitreolysis has been largely attempted through the use of enzymatic reagents. Ocriplasmin has been the only FDA-approved clinical reagent so far. Several adverse effects of ocriplasmin have emerged, however, and the search for alternative PVD-inducing reagents continues. Since i) collagen forms an important structural component of the vitreous, and ii) strong vitreo-retinal adhesions exist between the cortical vitreous and the internal limiting membrane (ILM) of the retina, an effective PVD-inducing reagent would require both, vitreous liquefaction, and concurrent dehiscence of vitreoretinal adhesion, without being toxic to retinal cells. We designed a combination of two reagents to achieve these two objectives; a triple helix-destabilizing collagen binding domain (CBD), and a fusion of RGD (integrin-binding) tripeptide with CBD (RCBD) to facilitate separation of posterior cortical vitreous from retinal surface. Based on <jats:italic>in vitro<\/jats:italic>, <jats:italic>ex-vivo<\/jats:italic>, and <jats:italic>in vivo<\/jats:italic> experiments, we show that a combination of CBD and RCBD displays potential for safe pharmacologic vitreolysis. Our findings assume significance in light of the fact that synthetic RGD-containing peptides have already been used for inhibition of tumor cell invasion. Proteins such as variants of collagen binding domains could have extended therapeutic uses in the future.<\/jats:p>","DOI":"10.1038\/s41598-020-64931-3","type":"journal-article","created":{"date-parts":[[2020,5,19]],"date-time":"2020-05-19T10:04:11Z","timestamp":1589882651000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Induction of posterior vitreous detachment (PVD) by non-enzymatic reagents targeting vitreous collagen liquefaction as well as vitreoretinal adhesion"],"prefix":"10.1038","volume":"10","author":[{"given":"Mithun","family":"Santra","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maryada","family":"Sharma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deeksha","family":"Katoch","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sahil","family":"Jain","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Uma Nahar","family":"Saikia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mangat R.","family":"Dogra","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manni","family":"Luthra-Guptasarma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,5,19]]},"reference":[{"key":"64931_CR1","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/S1569-2590(05)10007-X","volume":"10","author":"H Lund-Andersen","year":"2005","unstructured":"Lund-Andersen, H., Sebag, J., Sander, B. & La Cour, M. The vitreous. Advances in Organ Biology 10, 181\u2013194 (2005).","journal-title":"Advances in Organ Biology"},{"key":"64931_CR2","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1038\/eye.1987.45","volume":"1","author":"J Sebag","year":"1987","unstructured":"Sebag, J. Ageing of the vitreous. Eye 1, 254 (1987).","journal-title":"Eye"},{"key":"64931_CR3","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/S1350-9462(99)00016-6","volume":"19","author":"PN Bishop","year":"2000","unstructured":"Bishop, P. N. Structural macromolecules and supramolecular organisation of the vitreous gel. Prog. Retin. Eye Res. 19, 323\u201344 (2000).","journal-title":"Prog. Retin. Eye Res."},{"key":"64931_CR4","doi-asserted-by":"crossref","first-page":"1214","DOI":"10.1038\/eye.2008.21","volume":"22","author":"MM Le Goff","year":"2008","unstructured":"Le Goff, M. M. & Bishop, P. N. Adult vitreous structure and postnatal changes. Eye 22, 1214\u201322 (2008).","journal-title":"Eye"},{"key":"64931_CR5","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1159\/000353447","volume":"230","author":"MD De Smet","year":"2013","unstructured":"De Smet, M. D., Elkareem, A. M. & Zwinderman, A. H. The vitreous, the retinal interface in ocular health and disease. Ophthalmologica 230, 165\u201378 (2013).","journal-title":"Ophthalmologica"},{"key":"64931_CR6","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.ajo.2009.07.036","volume":"149","author":"NM Holekamp","year":"2010","unstructured":"Holekamp, N. M. The vitreous gel: more than meets the eye. Am J. Ophthalmol. 149, 32\u20136 (2010).","journal-title":"Am J. Ophthalmol."},{"key":"64931_CR7","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1007\/BF02160337","volume":"225","author":"J Sebag","year":"1987","unstructured":"Sebag, J. Age-related changes in human vitreous structure. Graefes Arch. Clin. Exp. Ophthalmol. 225, 89\u201393 (1987).","journal-title":"Graefes Arch. Clin. Exp. Ophthalmol."},{"key":"64931_CR8","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1007\/s00417-004-0980-1","volume":"242","author":"J Sebag","year":"2004","unstructured":"Sebag, J. Anomalous posterior vitreous detachment: a unifying concept in vitreo-retinal disease. Graefes Arch. Clin. Exp. Ophthalmol. 242, 690\u2013698 (2004).","journal-title":"Graefes Arch. Clin. Exp. Ophthalmol."},{"key":"64931_CR9","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1159\/000354547","volume":"230","author":"F Bandello","year":"2013","unstructured":"Bandello, F., La Spina, C., Iuliano, L., Fogliato, G. & Parodi, M. B. Review and perspectives on pharmacological vitreolysis. Ophthalmologica 230, 179\u2013185 (2013).","journal-title":"Ophthalmologica"},{"key":"64931_CR10","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.2147\/OPTH.S14840","volume":"5","author":"EW Schneider","year":"2011","unstructured":"Schneider, E. W. & Johnson, M. W. Emerging nonsurgical methods for the treatment of vitreomacular adhesion: a review. Clinical ophthalmology (Auckland, NZ) 5, 1151 (2011).","journal-title":"Clinical ophthalmology (Auckland, NZ)"},{"key":"64931_CR11","doi-asserted-by":"crossref","first-page":"1829","DOI":"10.1001\/archopht.1980.01020040681018","volume":"98","author":"LC Moorhead","year":"1980","unstructured":"Moorhead, L. C., Redburn, D. A., Kirkpatrick, D. S. & Kretzer, F. Bacterial collagenase: Proposed adjunct to vitrectomy with membranectomy. Arch. Ophthalmol. 98, 1829\u20131839 (1980).","journal-title":"Arch. Ophthalmol."},{"key":"64931_CR12","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1001\/archopht.1983.01040010267018","volume":"101","author":"LC Moorhead","year":"1983","unstructured":"Moorhead, L. C., Chu, H. H. & Garcia, C. A. Enzyme-assisted vitrectomy with bacterial collagenase: time course and toxicity studies. Arch. Ophthalmol. 101, 265\u2013274 (1983).","journal-title":"Arch. Ophthalmol."},{"key":"64931_CR13","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1097\/00006982-198500520-00007","volume":"5","author":"LC Moorhead","year":"1985","unstructured":"Moorhead, L. C. & Radtke, N. O. R. M. A. N. Enzyme-assisted vitrectomy with bacterial collagenase. Pilot human studies. Retina (Philadelphia, Pa. 5, 98\u2013100 (1985).","journal-title":"Pilot human studies. Retina (Philadelphia, Pa."},{"issue":"366-370","key":"64931_CR14","first-page":"1973","volume":"8","author":"R O'Neill","year":"1973","unstructured":"O\u2019Neill, R. The effects of bacterial collagenase in rabbit vitreous. Canad. J. Ophthal. 8(366-370), 1973 (1973).","journal-title":"Canad. J. Ophthal."},{"key":"64931_CR15","first-page":"802","volume":"47","author":"K Takahashi","year":"1993","unstructured":"Takahashi, K., Nakagawa, M. & Ninomiya, H. Enzyme-assisted vitrectomy with collagenase. Jpn. J. Clin. Ophthalmol. 47, 802\u2013803 (1993).","journal-title":"Jpn. J. Clin. Ophthalmol."},{"key":"64931_CR16","doi-asserted-by":"crossref","first-page":"2507","DOI":"10.1016\/j.febslet.2005.03.062","volume":"579","author":"JH Lee","year":"2005","unstructured":"Lee, J. H. et al. The FAXWXXT motif in the carboxyl terminus of Vibrio mimicus mEtalloprotease is involved in binding to collagen. FEBS Letters 579, 2507\u20132513 (2005).","journal-title":"FEBS Letters"},{"key":"64931_CR17","doi-asserted-by":"crossref","first-page":"3020","DOI":"10.1038\/sj.emboj.7600318","volume":"23","author":"L Chung","year":"2004","unstructured":"Chung, L. et al. Collagenase unwinds triple\u2010helical collagen prior to peptide bond hydrolysis. EMBO J. 23, 3020\u20133030 (2004).","journal-title":"EMBO J."},{"key":"64931_CR18","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1146\/annurev.cellbio.12.1.697","volume":"12","author":"E Ruoslahti","year":"1996","unstructured":"Ruoslahti, E. RGD and other recognition sequences for integrins. Annu. Rev. Cell Dev. Biol. 12, 697\u2013715 (1996).","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"64931_CR19","doi-asserted-by":"crossref","first-page":"2876","DOI":"10.1038\/nprot.2006.202","volume":"1","author":"NJ Greenfield","year":"2006","unstructured":"Greenfield, N. J. Using circular dichroism spectra to estimate protein secondary structure. Nature Protocols 1, 2876\u20132890 (2006).","journal-title":"Nature Protocols"},{"key":"64931_CR20","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1038\/nsmb.2127","volume":"18","author":"U Eckhard","year":"2011","unstructured":"Eckhard, U., Sch\u00f6nauer, E., N\u00fcss, D. & Brandstetter, H. Structure of collagenase G reveals a chew-and-digest mechanism of bacterial collagenolysis. Nat. Struct. Mol. Biol. 18, 1109\u20131114 (2011).","journal-title":"Nat. Struct. Mol. Biol."},{"key":"64931_CR21","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1006\/bbrc.2001.4713","volume":"283","author":"R Gayatri","year":"2001","unstructured":"Gayatri, R., Sharma, A. K., Rajaram, R. & Ramasami, T. Chromium (III)-induced structural changes and self-assembly of collagen. Biochem. Biophys. Res. Commun. 283, 229\u2013235 (2001).","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"64931_CR22","doi-asserted-by":"crossref","first-page":"3703","DOI":"10.1039\/C7TB03035E","volume":"6","author":"H Liang","year":"2018","unstructured":"Liang, H., Russell, S. J., Wood, D. J. & Tronci, G. A hydroxamic acid\u2013methacrylated collagen conjugate for the modulation of inflammation-related MMP upregulation. J. Mater. Chem. B. 6, 3703\u20133715 (2018).","journal-title":"J. Mater. Chem. B."},{"key":"64931_CR23","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1039\/C3SM52542B","volume":"10","author":"D Pelc","year":"2014","unstructured":"Pelc, D., Marion, S., Po\u017eek, M. & Basleti\u0107, M. Role of microscopic phase separation in gelation of aqueous gelatin solutions. Soft Matter 10, 348\u2013356 (2014).","journal-title":"Soft Matter"},{"key":"64931_CR24","doi-asserted-by":"crossref","first-page":"43336","DOI":"10.1074\/jbc.M407186200","volume":"279","author":"EM Tam","year":"2004","unstructured":"Tam, E. M., Moore, T. R., Butler, G. S. & Overall, C. M. Characterization of the distinct collagen binding, helicase and cleavage mechanisms of matrix mEtalloproteinase 2 and 14 (Gelatinase A and MT1-MMP) the differential roles of the mmp hemopexin c domains and the mmp-2 fibronectin type ii modules in collagen triple helicase activities. J. Biol. Chem. 279, 43336\u201343344 (2004).","journal-title":"J. Biol. Chem."},{"key":"64931_CR25","unstructured":"Lodish, H. et al. Collagen: the fibrous proteins of the matrix. Mol. Cell Biol., 4 (2000)."},{"key":"64931_CR26","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1167\/iovs.13-13026","volume":"55","author":"BA Filas","year":"2014","unstructured":"Filas, B. A., Zhang, Q., Okamoto, R. J., Shui, Y. B. & Beebe, D. C. Enzymatic degradation identifies components responsible for the structural properties of the vitreous body. Invest. Ophthalmol. Vis. Sci. 55, 55\u201363 (2014).","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"64931_CR27","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.1038\/s41433-019-0407-1","volume":"33","author":"M Grinton","year":"2019","unstructured":"Grinton, M. & Steel, D. H. \u201cCochrane Corner: Ocriplasmin-why isn\u2019t it being used more?\u201d. Nature Eye (London, England) 33, 1195\u20131197 (2019).","journal-title":"Nature Eye (London, England)"},{"key":"64931_CR28","first-page":"CD011874","volume":"10","author":"JE Neffendorf","year":"2017","unstructured":"Neffendorf, J. E., Kirthi, V., Pringle, E. & Jackson, T. L. Ocriplasmin for symptomatic vitreomacular adhesion. Cochrane Database of Systematic Reviews, 10, CD011874 (2017).","journal-title":"Cochrane Database of Systematic Reviews,"},{"key":"64931_CR29","doi-asserted-by":"crossref","first-page":"1267","DOI":"10.1080\/14740338.2016.1208169","volume":"15","author":"F Morescalchi","year":"2016","unstructured":"Morescalchi, F., Gambicorti, E., Duse, S., Costagliola, C. & Semeraro, F. From the analysis of pharmacologic vitreolysis to the comprehension of ocriplasmin safety. Expert. Opin. Drug. Saf. 15, 1267\u20131278 (2016).","journal-title":"Expert. Opin. Drug. Saf."},{"key":"64931_CR30","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1001\/jamaophthalmol.2013.8258","volume":"132","author":"MD Tibbetts","year":"2014","unstructured":"Tibbetts, M. D., Reichel, E. & Witkin, A. J. Vision loss after intravitreal ocriplasmin: correlation of spectral-domain optical coherence tomography and electroretinography. JAMA Ophthalmol. 132, 487\u2013490 (2014).","journal-title":"JAMA Ophthalmol."},{"key":"64931_CR31","doi-asserted-by":"crossref","first-page":"113","DOI":"10.3928\/23258160-20130313-02","volume":"44","author":"MD Ober","year":"2013","unstructured":"Ober, M. D. & Hariprasad, S. M. Ocriplasmin: Nonsurgical option for VMA and macular hole, but with potential barriers to practical use. Ophthalmic Surg. Lasers Imaging Retina 44, 113\u2013116 (2013).","journal-title":"Ophthalmic Surg. Lasers Imaging Retina"},{"key":"64931_CR32","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1097\/IAE.0000000000000667","volume":"35","author":"MW Johnson","year":"2015","unstructured":"Johnson, M. W., Fahim, A. T. & Rao, R. C. Acute ocriplasmin retinopathy. Retina (Philadelphia, Pa.) 35, 1055\u20131058 (2015).","journal-title":"Retina (Philadelphia, Pa.)"},{"key":"64931_CR33","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1001\/jamaophthalmol.2013.8142","volume":"132","author":"AT Fahim","year":"2014","unstructured":"Fahim, A. T., Khan, N. W. & Johnson, M. W. Acute panretinal structural and functional abnormalities after intravitreous ocriplasmin injection. JAMA Ophthalmol. 132, 484\u2013486 (2014).","journal-title":"JAMA Ophthalmol."},{"key":"64931_CR34","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1159\/000370024","volume":"5","author":"EK Chin","year":"2014","unstructured":"Chin, E. K. et al. Incomplete vitreomacular traction release using intravitreal ocriplasmin. Case Reports in Ophthalmology 5, 455\u2013462 (2014).","journal-title":"Case Reports in Ophthalmology"},{"key":"64931_CR35","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1076\/ceyr.25.6.333.14234","volume":"25","author":"LB Oliveira","year":"2002","unstructured":"Oliveira, L. B. et al. II RGD peptide-assisted vitrectomy tofacilitate induction of a posterior vitreous detachment: a new principle in pharmacological vitreolysis. Curr. Eye Res. 25, 333\u2013340 (2002).","journal-title":"Curr. Eye Res."},{"key":"64931_CR36","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1007\/s10529-008-9863-6","volume":"31","author":"DG Kim","year":"2009","unstructured":"Kim, D. G., Min, M. K., Ahn, S. C., Kim, J. K. & Kong, I. S. Expression of a fusion protein containing human epidermal growth factor and the collagen-binding domain of Vibrio\u00e1mimicus mEtalloprotease. Biotechnology letters 31, 259\u2013264 (2009).","journal-title":"Biotechnology letters"},{"key":"64931_CR37","doi-asserted-by":"crossref","first-page":"3589","DOI":"10.1089\/ten.tea.2008.0648","volume":"15","author":"Y Yang","year":"2009","unstructured":"Yang, Y. et al. Collagen-binding human epidermal growth factor promotes cellularization of collagen scaffolds. Tissue Engineering Part A 15, 3589\u20133596 (2009).","journal-title":"Tissue Engineering Part A"},{"key":"64931_CR38","doi-asserted-by":"crossref","first-page":"119","DOI":"10.4014\/jmb.1405.05073","volume":"25","author":"DG Kim","year":"2015","unstructured":"Kim, D. G., Kim, E. Y., Kim, Y. R. & Kong, I. S. Construction of chimeric human epidermal growth factor containing short collagen-binding domain moieties for use as a wound tissue healing agent. J. Microbiol. Biotechnol. 25, 119\u2013126 (2015).","journal-title":"J. Microbiol. Biotechnol."},{"key":"64931_CR39","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1089\/ten.tea.2012.0610","volume":"20","author":"R Visser","year":"2013","unstructured":"Visser, R. et al. A collagen-targeted biomimetic RGD peptide to promote osteogenesis. Tissue Engineering Part A 20, 34\u201344 (2013).","journal-title":"Tissue Engineering Part A"},{"key":"64931_CR40","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/S0092-8674(00)80622-4","volume":"101","author":"J Emsley","year":"2000","unstructured":"Emsley, J., Knight, C. G., Farndale, R. W., Barnes, M. J. & Liddington, R. C. Structural basis of collagen recognition by integrin \u03b12\u03b21. Cell 101, 47\u201356 (2000).","journal-title":"Cell"},{"key":"64931_CR41","doi-asserted-by":"crossref","first-page":"1723","DOI":"10.1002\/bit.22215","volume":"102","author":"R Sistiabudi","year":"2009","unstructured":"Sistiabudi, R., Paderi, J., Panitch, A. & Ivanisevic, A. Modification of native collagen with cell\u2010adhesive peptide to promote RPE cell attachment on Bruch\u2019s membrane. Biotechnol. Bioeng. 102, 1723\u20131729 (2009).","journal-title":"Biotechnol. Bioeng."},{"key":"64931_CR42","first-page":"499","volume":"101","author":"MA Zarbin","year":"2003","unstructured":"Zarbin, M. A. Analysis of retinal pigment epithelium integrin expression and adhesion to aged submacular human Bruch\u2019s membrane. Trans. Am. Ophthalmol. Soc. 101, 499\u2013520 (2003).","journal-title":"Trans. Am. Ophthalmol. Soc."},{"key":"64931_CR43","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1007\/s10856-016-5763-9","volume":"27","author":"N Davidenko","year":"2016","unstructured":"Davidenko, N. et al. Evaluation of cell binding to collagen and gelatin: a study of the effect of 2D and 3D architecture and surface chemistry. J. Mater. Sci. Mater. M. 27, 148 (2016).","journal-title":"J. Mater. Sci. Mater. M."},{"key":"64931_CR44","first-page":"5453","volume":"46","author":"HL Karageozian","year":"2005","unstructured":"Karageozian, H. L. Determine the safety and efficacy of Vitreosolve\u00ae administered intravitreally to induce a complete posterior vitreous detachment (PVD) in non-proliferative diabetic retinopathy human subjects. Invest. Ophthalmol. Vis. Sci. 46, 5453\u20135453 (2005).","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"64931_CR45","doi-asserted-by":"crossref","unstructured":"Sebag, J. Pharmacologic Vitreolysis. In Vitreous 799-815 (Springer, New York, NY, 2014).","DOI":"10.1007\/978-1-4939-1086-1_47"},{"key":"64931_CR46","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1038\/sj.eye.6702931","volume":"22","author":"W Chen","year":"2008","unstructured":"Chen, W. et al. Enzymatic vitreolysis with recombinant microplasminogen and tissue plasminogen activator. Eye 22, 300\u2013307 (2008).","journal-title":"Eye"},{"key":"64931_CR47","doi-asserted-by":"crossref","first-page":"792","DOI":"10.1097\/01.iae.0000244266.83395.16","volume":"26","author":"S Rizzo","year":"2006","unstructured":"Rizzo, S., Pellegrini, G., Benocci, F., Belting, C., Baicchi, U. & Vispi, M. Autologous plasmin for pharmacologic vitreolysis prepared 1 hour before surgery. Retina 26, 792\u2013796 (2006).","journal-title":"Retina"},{"key":"64931_CR48","doi-asserted-by":"crossref","first-page":"3286","DOI":"10.1167\/iovs.04-0026","volume":"45","author":"F Wang","year":"2004","unstructured":"Wang, F. et al. Safety and efficacy of dispase and plasmin in pharmacologic vitreolysis. Invest. Ophthalmol. Vis. Sci. 45, 3286\u20133290 (2004).","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"64931_CR49","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1080\/02713680600932142","volume":"31","author":"D Zhu","year":"2006","unstructured":"Zhu, D., Chen, H. & Xu, X. Effects of intravitreal dispase on vitreoretinal interface in rabbits. Curr. Eye Res. 31, 935\u2013946 (2006).","journal-title":"Curr. Eye Res."},{"key":"64931_CR50","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1167\/iovs.14-14934","volume":"56","author":"A Tiwari","year":"2015","unstructured":"Tiwari, A., Ram, J. & Luthra-Guptasarma, M. Targeting the fibronectin type III repeats in tenascin-C inhibits epithelial\u2013mesenchymal transition in the context of posterior capsular opacification. Invest. Ophthalmol. Vis. Sci. 56, 272\u2013283 (2015).","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"64931_CR51","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1111\/ceo.12307","volume":"42","author":"M Sharma","year":"2014","unstructured":"Sharma, M. et al. Pathological vitreous causes cell line\u2010derived (but not donorderived) retinal pigment epithelial cells to display proliferative vitreoretinopathy\u2010like features in culture. Clin. Exp. Ophthalmol. 42, 745\u2013760 (2014).","journal-title":"Clin. Exp. Ophthalmol."},{"key":"64931_CR52","doi-asserted-by":"crossref","first-page":"14285","DOI":"10.1074\/jbc.M109.087023","volume":"285","author":"YK Wang","year":"2010","unstructured":"Wang, Y. K. et al. Mechanistic insight into the function of the cterminal PKD domain of the collagenolytic serine protease deseasin MCP-01 from deep sea pseudoalteromonas sp. sm9913, binding of the PKD domain to collagen results in collagen swelling but does not unwind the collagen triple helix. J. Biol. Chem. 285, 14285\u201314291 (2010).","journal-title":"J. Biol. Chem."},{"key":"64931_CR53","doi-asserted-by":"crossref","first-page":"024002","DOI":"10.1117\/1.2907453","volume":"13","author":"M Asejczyk-Widlicka","year":"2008","unstructured":"Asejczyk-Widlicka, M., Schachar, R. & Pierscionek, B. K. Optical coherence tomography measurements of the fresh porcine eye and response of the outer coats of the eye to volume increase. J. Biomed. Opt. 13, 024002 (2008).","journal-title":"J. Biomed. Opt."}],"updated-by":[{"DOI":"10.1038\/s41598-020-69093-w","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2020,7,16]],"date-time":"2020-07-16T00:00:00Z","timestamp":1594857600000}}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-64931-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-64931-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-64931-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,6]],"date-time":"2022-12-06T11:39:30Z","timestamp":1670326770000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-64931-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,5,19]]},"references-count":53,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2020,12]]}},"alternative-id":["64931"],"URL":"https:\/\/doi.org\/10.1038\/s41598-020-64931-3","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,5,19]]},"assertion":[{"value":"27 November 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 March 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 May 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 July 2020","order":4,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Correction","order":5,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"An amendment to this paper has been published and can be accessed via a link at the top of the paper.","order":6,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"8250"}}