Lens regeneration using endogenous stem cells with gain of visual function

Lin, Haotian; Ouyang, Hong; Zhu, Jie; Huang, Shan; Liu, Zhenzhen; Chen, Shuyi; Cao, Guiqun; Li, Gen; Signer, Robert A.J.; Xu, Yanxin; Chung, Christopher; Zhang, Ying; Lin, Danni; Patel, Sheila V.; Wu, Frances; Cai, Huimin; Hou, Jiayi; Wen, Cindy; Jafari, Maryam; Liu, Xialin; Luo, Lixia; Zhu, Jin; Qiu, Austin; Hou, Rui; Chen, Baoxin; Chen, Jiangna; Granet, David B.; Heichel, Christopher W.D.; Shang, Fu; Li, Xuri; Krawczyk, Michał; Skowronska‐Krawczyk, Dorota; Wang, Yujuan; Shi, William Y.; Chen, Daniel; Zhong, Zheng; Zhong, Sheng; Zhang, Liangfang; Chen, Shaochen; Morrison, Sean J.; Maas, Richard L.; Zhang, Kang; Liu, Yizhi

doi:10.1038/nature17181

Cited by 177 publications

(151 citation statements)

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“…However, each year, millions of infants worldwide suffer from visual deprivation. These populations face the risk of irreversible amblyopia and numerous vision impairments [34][35][36]. Thus, it is important to investigate the mechanisms of environmental regulation of visual system development and its experience-dependent plasticity, which may provide further evidence to develop a comprehensive method for assessing the visual recovery potential in blind children.…”

Section: Discussionmentioning

confidence: 99%

Dynamic response to initial stage blindness in visual system development

et al. 2017

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Correspondence: Haotian Lin (gddlht@aliyun.com)Sensitive periods and experience-dependent plasticity have become core issues in visual system development. Converging evidence indicates that visual experience is an indispensable factor in establishing mature visual system circuitry during sensitive periods and the visual system exhibits substantial plasticity while facing deprivation. The mechanisms that underlie the environmental regulation of visual system development and plasticity are of great interest but need further exploration. Here, we investigated a unique sample of human infants who experienced initial stage blindness (beginning at birth and lasting for 2-8 months) before the removal of bilateral cataracts. Retinal thickness (RT), axial length (AL), refractive status, visual grating acuity and genetic integrity were recorded during the preoperative period or at surgery and then during follow-up. The results showed that the development of the retina is malleable and associated with external environmental influences. Our work supported that the retina might play critical roles in the development of the experience-dependent visual system and its malleability might partly contribute to the sensitive period plasticity.

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Section: Discussionmentioning

confidence: 99%

Dynamic response to initial stage blindness in visual system development

et al. 2017

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“…Pri novem načinu operacije prirojene sive mrene se ohrani večji del lečnih epitelnih celic, ki se nato razmnožujejo in oblikujejo funkcionalno lečo. Operacija se je izkazala za uspešno tako pri kuncih ter opicah kot tudi pri otrocih s prirojeno očesno mreno (15).…”

Section: Obnova Oz Regeneracija Očesne Lečeunclassified

“…V kontrolni skupini pa je imelo 25 otrok s prirojeno sivo mreno (50 oči) opravljeno standardno operacijo (15). Nov način operacije ima dve prednosti: precej se zmanjša velikost odstranjene lečne ovojnice, obenem pa se pomakne odprtina odstranjene lečne ovojnice iz osrednje vizualne osi k obodu.…”

Section: Obnova Oz Regeneracija Očesne Lečeunclassified

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Vloga lečnih epitelnih celic pri razvoju zamotnitve zadnje lečne ovojnice in pri obnovi leče po operaciji prirojene sive mrene

Andjelić¹

2017

SlovMedJour

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Vloga lečnih epitelnih celic pri razvoju zamotnitve zadnje lečne ovojnice in pri obnovi leče po operaciji prirojene sive mreneThe role of lens epithelial cells in the development of the posterior capsule opacification and in the lens regeneration after congenital cataract surgery Sofija andjelic IzvlečekNajpogostejši zaplet po operaciji sive mrene je zamotnitev zadnje lečne ovojnice (angl. posterior capsule opacification, PCO), ki pogosto povzroči poslabšanje vidne funkcije. Vzrok za nastanek PCO je razmnoževanje in selitev lečnih epitelnih celic, ki se med operacijo ne uspejo odstraniti in ostanejo na lečni ovojnici. PCO ima značilnost fibroze, ki se kaže z intenzivnejšim deljenjem, selitvijo, odlaganjem matriksa in spremembo oziroma prehodom v miofibroblaste.Presenetljivo rezultati najnovejših raziskav kažejo, da so lečne epitelne celice pomembne pri obnovi oz. regeneraciji leče pri novem načinu operacije prirojene sive mrene. Pri tem načinu se odstrani le 1-1,5 mm lečne ovojnice bolj lateralno, tako da ostane večji del lečnega epitela nepoškodovan. Nov način operacije se razlikuje od sedanjega, saj se pri njem ohranijo endogene lečne epitelne celice, ki se ne poskušajo odstraniti oz. uničiti. Lečne epitelne celice se tako lahko po operaciji razmnožujejo znotraj lečne ovojnice. Uspeli so doseči funkcionalno obnovo leče pri kuncih in opicah pa tudi pri otrocih s prirojeno očesno mreno. Za obnovo očesne leče je ključnega pomena pluripotentnost leč-nih epitelnih celic, ki imajo naravo zarodnih celic.Ex vivo kulture eksplantov lečnih ovojnic, na katerih so lečne epitelne celice, lahko uporabljamo za testiranje farmakoloških reagentov, s katerimi spodbujamo ali zaviramo rast lečnih epitelnih celic. Funkcionalnost celic in odgovore na farmakološke reagente lahko ovrednotimo z analizo znotraj-in zunajcelične signalizacije kalcija (Ca 2+ ).Spodbujanje rasti lečnih epitelnih celic je pomembno pri obnovi leče pri novem načinu operacije prirojene sive mrene, nasprotno pa je zaviranje rasti lečnih epitelnih celic pomembno pri prepreče-vanju razvoja PCO. Članek opisuje metode analize delovanja lečnih epitelnih celic, ki jih pridobimo pri operacijah sive mrene ter jih izvajamo v laboratoriju na Očesni kliniki UKC v Ljubljani. AbstractPosterior capsule opacification-PCO is the most common complication after cataract surgery. Proliferation and migration of lens epithelial cells that remain in the capsular bag following cataract surgery can lead to the development of PCO, which is the main cause of deterioration of visual function. PCO shows the classic features of fibrosis, including hyperproliferation, migration, deposition of matrix and its shrinkage and transdifferentiation into myofibroblast. Astonishingly, the results of recent research show the importance of lens epithelium for lens regeneration following congenital cataract surgery. New minimally invasive cataract surgery removes only 1-1.5 mm of lens epithelium more laterally, so the major part of the epithelium remains in the

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“…The mammalian lens also exhibits some level of regeneration ability through a different way, in which a new lens arises from residual lens epithelial cells (LECs) and requires a relatively intact lens capsular bag. The most recent work by Lin et al, 3 which successfully demonstrated lens regeneration taking place in the eyes of human infants, has ignited widespread interest. On the one hand, studies of the mechanism of lens regeneration can help to successfully rebuild a human lens after lens extraction or damage.…”

Section: Methodsmentioning

confidence: 99%

In Vivo Observation of Lens Regeneration in Rat Using Ultra-Long Scan Depth Optical Coherence Tomography

Zhou

Huang³

et al. 2016

Invest. Ophthalmol. Vis. Sci.

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In vivo observation of lens regeneration in rat using ultralong scan depth optical coherence tomography. Invest Ophthalmol Vis Sci. 2016;57:6615-6623. DOI: 10.1167/iovs.16-19363 PURPOSE. To evaluate morphologic changes of lens regeneration in rats in vivo after extracapsular lens extraction (ECLE) by ultra-long scan depth optical coherence tomography (UL-OCT). METHODS.A total of 42 Sprague-Dawley rats were used in this study. We performed ECLE on the right eyes of animals in the surgery group (n ¼ 34). Biomicroscopy and UL-OCT scans were carried out for the surgery group immediately (within 1 hour postoperatively) and at days 1 and 3, weeks 1 and 2, and months 1, 2, and 3 postoperatively. After in vivo examination, three animals of the surgery group were euthanized at each time point for histology study, while the other 10 animals were examined continuously at those time points. The regenerated lens was evaluated in OCT images at 2 and 3 months postoperatively. The control group consisted of eight untreated rats that had OCT examination at the age of 5 months.RESULTS. Lens regeneration could be observed from 2 weeks postoperatively. Regeneration was mainly at the peripheral capsular bag in the first month and central region thereafter. The average thickness of regenerated lenses was 2222 6 309 and 2324 6 352 lm at 2 and 3 months, respectively. Regeneration was faster in the first 2 months and slowed down thereafter. Although anterior capsule opening and posterior capsule adhesion and wrinkling existed, the regenerated lens still could form a relatively regular shape, however, the size was much smaller than that of the normal lenses from rats with the same age.CONCLUSIONS. Ultra-long OCT provides longitudinal data of the process of lens regeneration on a single individual rat in vivo, which may allow one to follow and compare the lens regenerative process under different interventions or therapy after ECLE in rats.

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Lens regeneration using endogenous stem cells with gain of visual function

Cited by 177 publications

References 29 publications

Dynamic response to initial stage blindness in visual system development

Dynamic response to initial stage blindness in visual system development

Vloga lečnih epitelnih celic pri razvoju zamotnitve zadnje lečne ovojnice in pri obnovi leče po operaciji prirojene sive mrene

In Vivo Observation of Lens Regeneration in Rat Using Ultra-Long Scan Depth Optical Coherence Tomography

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