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Prof Jane Sowden

Research Summary

My research group works on eye development and repair. Our aims are to define the molecular genetic pathways that regulate eye development, to understand how these pathways are disrupted in congenital eye disease, and to apply knowledge of retinal development to devise new strategies to repair and regenerate the diseased retina.

We analyse patient DNA samples to identify the genetic causes of childhood blindness. Between 9-20% of cases of childhood blindness in the UK involve structural malformations of the eye. These congenital eye abnormalities occur when the normal biological processes that form the eye before birth are disrupted. By correlating molecular diagnoses with clinical phenotype and outcomes our research aims to support clinical practice and management in paediatric ophthalmology.

A complex series of morphogenetic events and tissue interactions give rise to the embryonic optic cup, from which the mature eye globe subsequently develops before birth. Developmental eye anomalies, such as microphthalmia and coloboma, Axenfeld Rieger syndrome, corneal opacity and congenital glaucoma occur when gene mutations alter key developmental pathways. Mutation of the CHX10 gene, essential for expansion of the retinal progenitor cell population of the neural retina, was the first identified cause of non-syndromic microphthalmia. My lab studies models of abnormal eye development (e.g. Chx10-/- mice), in order to identify molecular pathways regulating neural progenitors destined to form the mature retina and anterior segment tissues.

Retinal progenitor cells undergo a finite number of cell divisions to produce the full complement of retinal neurons and glial cells during development. The adult retina is normally post-mitotic and is unable to replace neurons lost in disease. Retinal neurons die in retinal diseases such as retinitis pigmentosa and Lebers congenital amaurosis that involve loss of photoreceptor cells, or glaucoma involving loss of retinal ganglion cells, and the loss of vision is irreversible. We are exploring stem cell populations in the eye that may have the potential to repair the diseased retina. We showed that lack of Chx10 causes the adult retina to maintain a population of neural progenitors that can be expanded in neurosphere cultures in vitro. A different population of quiescent progenitor cells can be expanded from the ciliary epithelium of the eye. We are investigating whether such cells sources can be directed to produce new photoreceptors.

Working closely with Robin Ali's group at the UCL Institute of Ophthalmology we are developing cell transplantation approaches to repair the diseased retina. We have identified a population of rod photoreceptor precursor cells in the developing retina, defined by activation of the Nrl gene, that when transplanted into the mature retina are able to integrate and form new functional rod photoreceptors. By transplanting Crx-expressing precursors we have shown that transplantation of cone photoreceptors is also feasible. We have demonstrated that the diseased retina is capable of integrating new rod photoreceptors that restore some vision to blind mice.

Current work is focussed on isolating photoreceptor precursor cells from in vitro stem cell cultures, optimising conditions to promote the development of new cone photoreceptors cells, and defining the molecular properties that allow transplanted cells to effectively integrate and repair the retina.  


Research Activities

  • Development of novel therapies for the treatment of retinal degeneration
  • Eye Development and Repair
  • Stem Cell Therapy and Retinal Degeneration

Recent Publications

Displaying 50 most recent publications. For the full list please visit UCL Discovery

  1. Boucherie C,Mukherjee S,Henckaerts E,Thrasher AJ,Sowden JC,Ali RR (2013) Brief report: self-organizing neuroepithelium from human pluripotent stem cells facilitates derivation of photoreceptors. Stem Cells, 31(2), 408 - 414. 10.1002/stem.1268.
  2. West EL,Pearson RA,Duran Y,Gonzalez-Cordero A,MacLaren RE,Smith AJ,Sowden JC,Ali RR (2012) Manipulation of the recipient retinal environment by ectopic expression of neurotrophic growth factors can improve transplanted photoreceptor integration and survival. Cell Transplant, 21(5), 871 - 887. 10.3727/096368911X623871.
  3. Leng T,Marmor MF,Kellner U,Thompson DA,Renner AB,Moore W,Sowden JC (2012) Foveal cavitation as an optical coherence tomography finding in central cone dysfunction. Retina, 32(7), 1411 - 1419. 10.1097/IAE.0b013e318236e4ea.
  4. Prasov L,Masud T,Khaliq S,Mehdi SQ,Abid A,Oliver ER,Silva ED,Lewanda A,Brodsky MC,Borchert M,Kelberman D,Sowden JC,Dattani MT,Glaser T (2012) ATOH7 mutations cause autosomal recessive persistent hyperplasia of the primary vitreous. Hum Mol Genet, 21(16), 3681 - 3694. 10.1093/hmg/dds197.
  5. Park S,Jamshidi Y,Vaideanu D,Fraser S,Sowden JC (2012) Common TGFβ2, BMP4, and FOXC1 variants are not associated with primary open-angle glaucoma. Mol Vis, 18, 1526 - 1539.
  6. 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 (2012) Restoration of vision after transplantation of photoreceptors. Nature, 485(7396), 99 - 103. 10.1038/nature10997.
  7. West EL,Gonzalez-Cordero A,Hippert C,Osakada F,Martinez-Barbera JP,Pearson RA,Sowden JC,Takahashi M,Ali RR (2012) Defining the integration capacity of embryonic stem cell-derived photoreceptor precursors. Stem Cells, 30(7), 1424 - 1435. 10.1002/stem.1123.
  8. Lange CA,Luhmann UF,Mowat FM,Georgiadis A,West EL,Abrahams S,Sayed H,Powner MB,Fruttiger M,Smith AJ,Sowden JC,Maxwell PH,Ali RR,Bainbridge JW (2012) Von Hippel-Lindau protein in the RPE is essential for normal ocular growth and vascular development. Development, 139(13), 2340 - 2350. 10.1242/dev.070813.
  9. Shah SP,Taylor AE,Sowden JC,Ragge N,Russell-Eggitt I,Rahi JS,Gilbert CE,Surveillance of Eye Anomalies Special Interest Group (2012) Anophthalmos, microphthalmos, and Coloboma in the United kingdom: clinical features, results of investigations, and early management. Ophthalmology, 119(2), 362 - 368. 10.1016/j.ophtha.2011.07.039.
  10. Webb TR,Matarin M,Gardner JC,Kelberman D,Hassan H,Ang W,Michaelides M,Ruddle JB,Pennell CE,Yazar S,Khor CC,Aung T,Yogarajah M,Robson AG,Holder GE,Cheetham ME,Traboulsi EI,Moore AT,Sowden JC,Sisodiya SM,Mackey DA,Tuft SJ,Hardcastle AJ (2012) X-linked megalocornea caused by mutations in CHRDL1 identifies an essential role for ventroptin in anterior segment development. Am J Hum Genet, 90(2), 247 - 259. 10.1016/j.ajhg.2011.12.019.
  11. West EL,Gonzalez-Cordero A,Hippert C,Duran Y,Pearson RA,Sowden JC,Ali RR (2011) Embryonic stem cell-derived retinal cells transplanted to the adult retina HUM GENE THER, 22(10), A79 - A80.
  12. Shah SP,Taylor AE,Sowden JC,Ragge NK,Russell-Eggitt I,Rahi JS,Gilbert CE,Surveillance of Eye Anomalies (SEA-UK) Special Interest Group (2011) Anophthalmos, microphthalmos, and typical coloboma in the United Kingdom: a prospective study of incidence and risk. Invest Ophthalmol Vis Sci, 52(1), 558 - 564. 10.1167/iovs.10-5263.
  13. Kelberman D,Islam L,Jacques TS,Russell-Eggitt I,Bitner-Glindzicz M,Khaw PT,Nischal KK,Sowden JC (2011) CYP1B1-related anterior segment developmental anomalies novel mutations for infantile glaucoma and von Hippel's ulcer revisited. Ophthlamology, 118(9), 1865 - 1873.
  14. Decembrini S,Cananzi M,Gualdoni S,Battersby A,Allen N,Pearson RA,Ali RR,De Coppi P,Sowden JC (2011) Comparative analysis of the retinal potential of embryonic stem cells and amniotic fluid-derived stem cells. Stem Cells Dev, 20(5), 851 - 863. 10.1089/scd.2010.0291.
  15. Kelberman D,Islam L,Jacques TS,Russell-Eggitt I,Bitner-Glindzicz M,Khaw PT,Nischal KK,Sowden JC (2011) CYP1B1-related anterior segment developmental anomalies novel mutations for infantile glaucoma and von Hippel's ulcer revisited. Ophthalmology, 118(9), 1865 - 1873. 10.1016/j.ophtha.2011.01.044.
  16. Mataftsi A,Islam L,Kelberman D,Sowden JC,Nischal KK (2011) Chromosome abnormalities and the genetics of congenital corneal opacification. Mol Vis, 17, 1624 - 1640.
  17. Gualdoni S,Baron M,Lakowski J,Decembrini S,Pearson RA,Ali RR,Sowden JC (2011) Isolation and culture of adult ciliary epithelial cells, previously identified as retinal stem cells, and retinal progenitor cells. Curr Protoc Stem Cell Biol, Chapter 1, Unit - 1H.4. 10.1002/9780470151808.sc01h04s19.
  18. Lakowski J,Han YT,Pearson RA,Gonzalez-Cordero A,West EL,Gualdoni S,Barber AC,Hubank M,Ali RR,Sowden JC (2011) Effective transplantation of photoreceptor precursor cells selected via cell surface antigen expression. Stem Cells, 29(9), 1391 - 1404. 10.1002/stem.694.
  19. Boucherie C,Sowden JC,Ali RR (2011) Induced pluripotent stem cell technology for generating photoreceptors. Regen Med, 6(4), 469 - 479. 10.2217/rme.11.37.
  20. Ali RR,Sowden JC (2011) Regenerative medicine: DIY eye. Nature, 472(7341), 42 - 43. 10.1038/472042a.
  21. Kelberman D,Islam L,Holder SE,Jacques TS,Calvas P,Hennekam RC,Nischal KK,Sowden JC (2011) Digenic inheritance of mutations in FOXC1 and PITX2 : correlating transcription factor function and Axenfeld-Rieger disease severity. Hum Mutat, 32(10), 1144 - 1152. 10.1002/humu.21550.
  22. Gualdoni S,Baron M,Lakowski J,Decembrini S,Smith AJ,Pearson RA,Ali RR,Sowden JC (2010) Adult ciliary epithelial cells, previously identified as retinal stem cells with potential for retinal repair, fail to differentiate into new rod photoreceptors. Stem Cells, 28(6), 1048 - 1059. 10.1002/stem.423.
  23. Lakowski J,Baron M,Bainbridge J,Barber AC,Pearson RA,Ali RR,Sowden JC (2010) Cone and rod photoreceptor transplantation in models of the childhood retinopathy Leber congenital amaurosis using flow-sorted Crx-positive donor cells Hum.Mol.Genet, 19, 4545 - 4559.
  24. West EL,Gonzalez CA,Pearson RA,Barber A,Sowden JC,Ali RR (2010) Immune Responses Affect the Survival of Integrated Photoreceptor Precursors Transplanted to the Adult Murine Retina HUMAN GENE THERAPY, 21(4), 513 - 513.
  25. West EL,Pearson RA,Barker SE,Luhmann UF,Maclaren RE,Barber AC,Duran Y,Smith AJ,Sowden JC,Ali RR (2010) Long-term survival of photoreceptors transplanted into the adult murine neural retina requires immune modulation. Stem Cells, 28(11), 1997 - 2007. 10.1002/stem.520.
  26. Pearson RA,Barber AC,West EL,MacLaren RE,Duran Y,Bainbridge JW,Sowden JC,Ali RR (2010) Targeted disruption of outer limiting membrane junctional proteins (Crb1 and ZO-1) increases integration of transplanted photoreceptor precursors into the adult wild-type and degenerating retina. Cell Transplant, 19(4), 487 - 503. 10.3727/096368909X486057.
  27. Mataftsi A,Sowden JC,Nischal KK (2010) Atypical Peters plus syndrome with new associations. J AAPOS, 14(6), 560 - 561. 10.1016/j.jaapos.2010.09.001.
  28. Park S,Jamshidi Y,Vaideanu D,Bitner-Glindzicz M,Fraser S,Sowden JC (2009) Genetic risk for primary open-angle glaucoma determined by LMX1B haplotypes Invest Ophthalmol.Vis.Sci., 50(4), 1522 - 1530.
  29. Barber AC,MacLaren RE,Bainbridge JWB,Sowden J,Ali RR,Pearson RA (2009) Barriers to Integration of Transplanted Photoreceptor Precursors: Gliosis in Crb1rd8/rd8 and Rho-/- Mouse Models of Retinal Degeneration Invest. Ophthalmol. Vis. Sci., 50(5), 689-.
  30. Lakowski J,Baron M,Bainbridge J,Barber A,Pearson RA,Ali RR,Sowden JC (2009) Generation of New Cone and Rod Photoreceptors in the Adult Retina by Transplantation of Crx-Positive Precursor Cells Invest. Ophthalmol. Vis. Sci., 50(5), 5139-.
  31. Shah SP,Taylor AE,Rahi J,Sowden JC,Ragge N,Russell-Eggitt I,Gilbert CE,SEA-UK Special Interest Group (2009) Congenital Eye Anomalies: An Epidemiological Study in the United Kingdom Invest. Ophthalmol. Vis. Sci., 50(5), 4688-.
  32. Taylor A,Shah S,Rahi J,Sowden J,Russell- Eggitt I,Ragge N,Gilbert C (2009) Typical Coloboma in the UK: A Population Based Study Invest. Ophthalmol. Vis. Sci., 50(5), 4685-.
  33. West EL,Pearson RA,MacLaren RE,Sowden JC,Ali RR (2009) Cell transplantation strategies for retinal repair Prog.Brain Res., 175, 3 - 21.
  34. Barber AC,Bainbridge JWB,Sowden JC,Ali RR,Pearson RA (2009) The role of gliosis and extracellular matrix proteins in rod photoreceptor precursor transplantation in the degenerating retina Mechanisms of Development, 126, S245 - S245.
  35. Behesti H,Papaioannou VE,Sowden JC (2009) Loss of Tbx2 delays optic vesicle invagination leading to small optic cups Dev Biol.
  36. Kokkinopoulos I,Pearson RA,Macneil A,Dhomen NS,Maclaren RE,Ali RR,Sowden JC (2008) Isolation and characterisation of neural progenitor cells from the adult Chx10(orJ/orJ) central neural retina Molecular and Cellular Neuroscience, 38(3), 359 - 373. 10.1016/j.mcn.2008.03.008.
  37. Sowden JC (2008) The Development of the Eye.
  38. Pocock R,Mione M,Hussain S,Maxwell S,Pontecorvi M,Aslam S,Gerrelli D,Sowden J,Woollard A (2008) Neuronal function of Tbx20 conserved from nematodes to vertebrates Developmental Biology, 317(2), 671 - 685.
  39. West EL,Pearson RA,Tschernutter M,Sowden JC,Maclaren RE,Ali RR (2008) Pharmacological disruption of the outer limiting membrane leads to increased retinal integration of transplanted photoreceptor precursors Exp.Eye Res., 86(4), 601 - 611.
  40. West EL,Pearson RA,Duran Y,Luhmann UFO,Barker SE,Smith AJ,Sowden JC,MacLaren RE,Ali RR (2008) Over-Expression of Developmentally Regulated Neurotrophins in the Adult Mouse Retina to Facilitate Integration of Transplanted Photoreceptor Precursor Cells Invest. Ophthalmol. Vis. Sci., 49(5), 4279-.
  41. Chanda B,Asai-Coakwell M,Ye M,Mungall AJ,Barrow M,Dobyns WB,Behesti H,Sowden JC,Carter NP,Walter MA,Lehmann OJ (2008) A novel mechanistic spectrum underlies glaucoma-associated chromosome 6p25 copy number variation. Hum Mol Genet, 17(22), 3446 - 3458. 10.1093/hmg/ddn238.
  42. Pearson RA,West EL,Duran Y,Georgiadis A,Barber A,Sowden JC,MacLaren RE,Ali RR (2008) Enhanced Integration of Transplanted Photoreceptor Precursors Following Molecular and Genetic Disruption of the Outer Limiting Membrane Invest. Ophthalmol. Vis. Sci., 49(5), 5036-.
  43. Park S,Jamshidi Y,Vaideanu D,Fraser S,Sowden JC (2008) An Investigation of the Developmental Glaucoma Genes as Genetic Risk Factors in Ocular Hypertension and Primary Open Angle Glaucoma Invest. Ophthalmol. Vis. Sci., 49(5), 5125-.
  44. Chanda B,Asai-Coakwell M,Sowden JC,Walter MA,Lehmann OJ (2008) A Novel Mechanistic Spectrum Underlies Glaucoma-Associated Chromosome 6p25 Copy Number Variations Invest. Ophthalmol. Vis. Sci., 49(5), 1654-.
  45. West EL,Pearson RA,Duran Y,Luhmann UFO,Barker SE,Smith AJ,Sowden JC,MacLaren RE,Ali RR (2008) Overexpression of developmentally regulated neurotrophins in the adult mouse retina to facilitate integration of transplanted photoreceptor precursor cells HUMAN GENE THERAPY, 19(4), 412 - 412.
  46. Ali RR,Pearson RA,MacLaren RE,West E,MacNeil A,Douglas RH,Salt TE,Akimoto M,Swaroop A,Sowden JC (2007) Kinetics of Rod Photoreceptor Precursor Integration Following Transplantation in the Adult Mouse Retina Investigative Ophthalmology & Visual Science, 48(5), 5653.
  47. Ali RR,Pearson RA,MacLaren RE,West E,MacNeil A,Douglas RH,Salt TE,Akimoto M,Swaroop A,Sowden JC (2007) Kinetics of Rod Photoreceptor Precursor Integration Following Transplantation in the Adult Mouse Retina Invest. Ophthalmol. Vis. Sci., 48(5), 5653-.
  48. Chanda B,Asai-Coakwell M,Ye M,Sowden JC,Walter MA,Lehmann OJ (2007) Progress Determining the Mechanism of Segmental Duplication and Deletion in Axenfeld Rieger Phenotypes Invest. Ophthalmol. Vis. Sci., 48(5), 5598-.
  49. MacNeil A,Pearson RA,MacLaren RE,Buch PK,Smith AJ,Sowden JC,Ali RR (2007) Comparative Analysis of Neural Stem Cells Isolated From the Iris, Pars Plana and Ciliary Body of the Porcine Eye Invest. Ophthalmol. Vis. Sci., 48(5), 2906-.
  50. West EL,Pearson RA,Sowden JC,MacLaren RE,Ali RR (2007) The Outer Limiting Membrane as a Barrier to Photoreceptor Integration, After Transplantation to the Subretinal Space of the Adult Mouse Invest. Ophthalmol. Vis. Sci., 48(5), 5080-.

Qualifications

  • 1991: Doctor of Philosophy, University College London
  • 1987: Bachelor of Arts (Honours), University of Oxford

Keywords

  • Retinal development
  • Age-related macular degeneration
  • Blindness
  • Cell culture
  • Cell transplantation
  • Confocal microscopy
  • Development
  • Differentiation
  • Eye development
  • Gene expression
  • Gene expression profiling - tissue level
  • Genetically encoded reporters/indicators
  • Genetics
  • Genomic analyses
  • Glaucoma
  • Glaucoma
  • Histology
  • Immunohistochemistry
  • Leber's congenital amaurosis
  • Light microscopic techniques
  • Microarrays
  • Mouse
  • Neural stem cells
  • Neuron
  • Progenitors
  • Proliferation
  • Repair
  • Retina
  • Retinal development and disease
  • Retinitis pigmentosa
  • Stem cells
  • Transgenic mice
  • Vision
  • Vision Research at UCL
  • congenital eye disease
  • retinal degeneration
  • retinal stem cells
  • stem cell therapy
  • stem cells for regeneration and repair