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Supervisors: Professor Jane Sowden and Professor Nicola Elvassore
Background:
Children affected by inherited retinal degenerative diseases have few treatment options. Irreversible blindness results from the progressive death of the light-sensing photoreceptor cells in the outer part of the retina. Stem cells and tissue engineering offer a potential way to regenerate the damaged retinal tissue and preserve sight. Towards this goal, pre-clinical studies have showed that photoreceptor cell transplantation restores some visual function and recent clinical trials showed that it is safe to transplant stem cell progeny into the eye 1,2.
Aims/Objectives:
In this project we propose to investigate novel micro-engineering approaches to create a human retinal tissue patch that could be used to repair the retina. As the inner retinal neurons and optic nerve that transmit visual information to the brain remain largely intact, connecting a new patch of photoreceptors could restore light perception to people with retinal dystrophy. Human pluripotent stem cells will be differentiated in vitro into 3D retinal organoids that resemble developing retinal tissue and produce new cone and rod photoreceptor cells 3,4. We will investigate in laboratory studies different approaches to grow polarised layers of photoreceptor cells on novel microengineered biocompatible scaffolds 5. These studies will aim to establish an in vitro system that could be used to prepare a viable and functional photoreceptor cell patch that could ultimately be used to repair damaged retinal tissue.
References:
1. Restoration of vision after transplantation of photoreceptors. Pearson RA, Barber AC, Rizzi M, Hippert C, Xue T, West EL, Duran Y, Smith AJ, Chuang JZ, Azam SA, Luhmann UF, Benucci A, Sung CH, Bainbridge JW, Carandini M, Yau KW, Sowden JC , Ali RR. Nature, 2012;485:99-103.
2. Phase 1 clinical study of an embryonic stem cell-derived retinal pigment epithelium patch in age-related macular degeneration. da Cruz L, Fynes K, Georgiadis O, Kerby J, Luo YH, Ahmado A, Vernon A, Daniels JT, Nommiste B, Hasan SM, Gooljar SB, Carr AF, Vugler A, Ramsden CM, Bictash M, Fenster M, Steer J, Harbinson T, Wilbrey A, Tufail A, Feng G, Whitlock M, Robson AG, Holder GE, Sagoo MS, Loudon PT, Whiting P, Coffey PJ. Nat Biotechnol . 2018 Apr;36(4):328-337.
3. Isolation and Comparative Transcriptome Analysis of Human Fetal and iPSC-Derived Cone Photoreceptor Cells. Welby E, Lakowski J, Di Foggia V, Budinger D, Gonzalez-Cordero A, Lun ATL, Epstein M, Patel A, Cuevas E, Kruczek K, Naeem A, Minneci F, Hubank M, Jones DT, Marioni JC, Ali RR, Sowden JC . Stem Cell Reports , 2017;9(6):1898-1915.
4. Isolation of human photoreceptor precursors via a cell surface marker panel from stem cell-derived retinal organoids and fetal retinae. Lakowski J, Welby E, Budinger D, Di Marco F, Di Foggia V, Bainbridge JWB, Wallace K, Gamm DM, Ali RR, Sowden JC . Stem Cells , 2018;36:709-722.
5. Photocrosslinked hydrogels from coumarin derivatives of hyaluronic acid for tissue engineering applications. Beninatto R, Barbera C, De Lucchi O, Borsato G, Serena E, Guarise C, Pavan M, Luni C, Martewicz S, Galesso D, Elvassore N. Mater Sci Eng C Mater Biol Appl. 2019 Mar;96:625-634.