Human neural retinal transplantation.

PURPOSE A pilot study of human neural retinal transplantation was undertaken to investigate three major issues: whether a safe surgical procedure could be devised for transplantation of neural retinal tissue into the subretinal space, whether the transplant would be accepted in the subretinal space, and whether an improvement in vision could be achieved. METHODS Eight patients with bare light perception (LP) vision due to retinitis pigmentosa (RP) and one patient with bare LP vision due to advanced neovascular age-related macular degeneration (AMD) received subretinal transplants of human fetal retinal microaggregate suspensions without postoperative systemic immunosuppression. The patient with AMD also received a fetal retinal sheet transplant. The ages of the patients ranged from 31 to 94 years (median, 55 years). The pre- and postoperative evaluations included visual function testing, detailed fundus examinations, fundus photography, fluorescein angiography, macular perimetry using a scanning laser ophthalmoscope (SLO), and full field and focal electroretinograms (ERGs). RESULTS Three of the eight RP patients demonstrated possible improved light sensitivity during the initial months of follow-up. However, visual improvement disappeared between 3 and 13 months of follow-up. After transplantation, no subject showed any changes in the ERG recordings or SLO macular perimetry relative to their preoperative baseline. No patient experienced a retinal detachment, infection, or extensive bleeding. None of the patients developed retinal vasculitis or intraocular inflammation. In one RP patient, fluorescein angiography and fundus photography documented the formation and maturation of new host retinal vessels in the area of the transplant. CONCLUSIONS Transplantation of fetal retinal photoreceptor suspensions into the subretinal space was achieved safely in nine subjects. Although a definite positive effect on visual function could not be demonstrated, the apparent high tolerance for graft tissue is promising for future efforts in the field of neural retinal transplantation.

[1]  H. Kaplan,et al.  Human photoreceptor transplantation in retinitis pigmentosa. A safety study. , 1997, Archives of ophthalmology.

[2]  R. Aramant,et al.  Donor age influences on the success of retinal grafts to adult rat retina. , 1988, Investigative ophthalmology & visual science.

[3]  B. Ehinger,et al.  Transplant of full-thickness embryonic rabbit retina using pars plana vitrectomy. , 1998, Retina.

[4]  Roy Pe,et al.  Retinal transplantation from fetal to maternal mammalian eye. , 1959 .

[5]  J. Ison,et al.  Intraretinal grafting restores visual function in light-blinded rats. , 1991, Neuroreport.

[6]  R. Aramant,et al.  Fiber and Synaptic Connections between Embryonic Retinal Transplants and Host Retina , 1995, Experimental Neurology.

[7]  D. Diloreto,et al.  Neither intraocular grafts of retinal cell homogenates nor live non-retinal neurons produce behavioral recovery in rats with light-damaged retinas. , 1995, Cell transplantation.

[8]  H. M. Petry,et al.  Preliminary report: indications of improved visual function after retinal sheet transplantation in retinitis pigmentosa patients. , 1999, American journal of ophthalmology.

[9]  T. Friberg,et al.  Natural course of retinitis pigmentosa over a three-year interval. , 1985, American journal of ophthalmology.

[10]  M. Cerro,et al.  A new procedure for multiple intraretinal transplantation into mammalian eyes , 1992, Journal of Neuroscience Methods.

[11]  P. Gouras,et al.  Long-term photoreceptor transplants in dystrophic and normal mouse retina. , 1994, Investigative ophthalmology & visual science.

[12]  S. Ball,et al.  Photoreceptor function of retinal transplants implicated by light-dark shift of S-antigen and rod transducin , 1999, Vision Research.

[13]  P. Gouras,et al.  Survival and Synapse Formation of Transplanted Rat Rods , 1991, Journal of neural transplantation & plasticity.

[14]  J E Turner,et al.  Newborn rat retinal cells transplanted into a retinal lesion site in adult host eyes. , 1986, Brain research.

[15]  A. Adolph,et al.  Function and Structure in Retinal Transplants , 1994, Journal of neural transplantation & plasticity.

[16]  Peter Gouras,et al.  Retinal cell transplantation in the macula: New techniques , 1996, Vision Research.

[17]  A. Adolph,et al.  Ultrastructural Circuitry in Retinal Cell Transplants to Rat Retina , 1994, Journal of neural transplantation & plasticity.

[18]  Stanley J. Wiegand,et al.  Intraretinal Transplantation for Rod-Cell Replacement in Light-Damaged Retinas , 1989, Journal of neural transplantation.

[19]  B. Ehinger,et al.  Graft-host connections in long-term full-thickness embryonic rabbit retinal transplants. , 1999, Investigative ophthalmology & visual science.

[20]  P. Gouras,et al.  Transplantation of photoreceptors labeled with tritiated thymidine into RCS rats. , 1991, Investigative ophthalmology & visual science.

[21]  S. E. Hughes,et al.  Transplantation of photoreceptors to light-damaged retina. , 1989, Investigative ophthalmology & visual science.

[22]  D. Diloreto,et al.  Storage of Human Fetal Retina in Optisol Prior to Subretinal Transplantation , 1996 .

[23]  A. Adolph,et al.  Ultrastructure of human retinal cell transplants with long survival times in rats. , 1991, Experimental eye research.

[24]  B. Ehinger,et al.  Cellular Organization in Retinal Transplants Using Cell Suspensions or Fragments of Embryonic Retinal Tissue , 1993, Cell transplantation.

[25]  R. Lund,et al.  Visual information processing by intracerebral retinal transplants in rats , 1994, Eye.

[26]  R. Aramant,et al.  Intact sheets of fetal retina transplanted to restore damaged rat retinas. , 1998, Investigative ophthalmology & visual science.

[27]  P. Gouras,et al.  Monitoring photoreceptor transplants with nuclear and cytoplasmic markers , 1992, Experimental Neurology.

[28]  K. Tansley.  The development of the rat eye in graft. , 1946, The Journal of experimental biology.

[29]  S. Wiegand,et al.  Intraocular retinal transplants. , 1985, Investigative ophthalmology & visual science.

[30]  M. Cerro,et al.  The Transplantation of Human Fetal Neuroretinal Cells in Advanced Retinitis Pigmentosa Patients: Results of a Long-Term Safety Study , 1999, Experimental Neurology.