Experimental and Surgical Aspects of Retinal Pigment Epithelial Cell Transplantation

doi:10.1016/S0955-3681(13)80263-8

European journal of Implant and Refractive Surgery

Volume 5, Issue 2, June 1993, Pages 128-132

$European journal of Implant and Refractive Surgery$

https://doi.org/10.1016/S0955-3681(13)80263-8 Get rights and content

Abstract

OBJECTIVES: To discuss the current status of experimental studies on transplantation of the retinal pigment epithelium (RPE), and surgical results on the excision of subfoveal choroidal new vessel membranes in age-related macular degeneration (AMD) and presumed ocular histoplasmosis (POHS). STUDY DESIGN: Experimental study on transplantation of the RPE in organ culture and in vivo, and results of a prospective series on surgical excision of choroidal neovascularization. SETTING: Department of Ophthalmology and Visual Sciences, Washington University School of Medicine. PATIENTS: Patients with subfoveal neovascular membranes secondary to AMD and POHS. MAIN OUTCOME MEASURES: Histological results on transplantation of the RPE onto Bruch's membrane in experimental animal models, and visual results on surgical excision of subfoveal choroidal neovascularization in patients with AMD and POHS. RESULTS: We have demonstrated that the RPE monolayer can heal after surgical debridement in the experimental animal, and retinal recovery occurs after healing of the RPE monolayer. We have demonstrated that RPE can reattach to healthy Bruch's membrane in vitro, and have performed RPE transplantation into the subretinal space in vivo. CONCLUSIONS: We are currently involved in a multifaceted approach aimed at RPE transplantation and surgical reconstruction of the photoreceptor-RPE-Bruch's membrane interface. We are hopeful that our approach will be applicable to the clinical problem of subfoveal choroidal new vessel membranes in AMD and POHS, in addition to the broad applicability of RPE transplantation to patients with diseases arising from primary RPE dysfunction.

References (30)

L Li et al.
Long-term rescue of photoreceptor cells in the retinas of RCS dystrophic rats by RPE transplants
Progress in Brain Research
(1990)
L Li et al.
Inherited retinal dystrophy in the RCS rat: prevention of photoreceptor degeneration by pigment epithelial cell transplantation
Exp. Eye Res.
(1988)
L Li et al.
Transplantation of retinal pigment epithelial cells to immature and adult rat hosts: short- and longterm survival characteristics
Exp. Eye Res.
(1988)
HJ Sheedlo et al.
Functional and structural characteristics of photoreceptor cells rescued in RPE-cell grafted retinas of RCS dystrophic rats
Exp. Eye Res.
(1989)
AS Berger et al.
Clinical experience with the surgical removal of subfoveal neovascular membranes. Short-term postoperative results
Ophthalmology
(1992)
MA Thomas et al.
Surgical management of subfoveal choroidal neovascularization
Ophthalmology
(1992)
M Brittis et al.
Autotransplantation of cultured retinal epithelium to Bruch's membrane in the rabbit eye
Transplantation Proceedings
(1987)
P Gouras et al.
Transplantation of cultured human retinal epithelium to Bruch's membrane of the owl monkey's eye
Curr. Eye Res.
(1985)
P Gouras et al.
Transplantation of cultured human retinal cells to monkey retina
An. Acad. brasil Cienc.
(1984)
P Gouras et al.
Transplantation of cultured retinal epithelium

P Gouras et al.

Transplantation of retinal epithelium prevents photoreceptor degeneration in the RCS rat

P Gouras et al.

Transplantation of retinal epithelial cells

Invest. Ophthalmol. Vis. Sci.

(1989)

C Lane et al.

Retinal pigment epithelial transplantation: technique and possible applications

Advances in the Biosciences

(1987)

C Lane et al.

Transplantation of retinal pigment epithelium in the miniature pig

Invest. Ophthalmol. Vis. Sci.

(1988)

C Lane et al.

Transplantation of retinal pigment epithelium using a pars plana approach

Eye

(1989)

Cited by (24)

Adult Retinal Pigment Epithelial Transplantation in Exudative Age-related Macular Degeneration
2007, American Journal of Ophthalmology
Citation Excerpt :
Histology of an eye from a patient who had undergone surgical excision of a choroidal neovascular membrane in AMD revealed incomplete resurfacing of the RPE defect after surgery.32 Similarly, pharmacologic damage to the RPE or surgical removal of the RPE leads to atrophy of the choriocapillaris in animal models.22 On the basis of these observations, it is reasonable to hypothesize that placement of healthy RPE under the center of the fovea may prevent postoperative atrophy of the subfoveal choriocapillaris, or possibly regenerate missing choriocapillaris from existing choroidal vessels, and improve the visual prognosis in this disease.
To improve visual function by retinal pigment epithelial (RPE) cell transplantation and systemic immunosuppression at the time of surgical removal of subfoveal choroidal neovascularization in exudative age-related macular degeneration (AMD).
An interventional case series of RPE transplantation in exudative AMD.
Twelve patients (one eye only) underwent subfoveal membranectomy with transplantation of a sheet of adult human allogeneic RPE cells at a single institution and were followed for one year. Eligibility criteria included age >60, best-corrected acuity ≤20/63 and subfoveal neovascularization ≤9 disk areas on preoperative fluorescein angiography. All patients were started on triple immunosuppression postoperatively. The primary outcome measure was best-corrected vision, with contrast sensitivity and reading speed as secondary outcome measures.
The best-corrected visual acuity (P = .085), contrast sensitivity (P = .204), and the reading speed (P = .077) did not change significantly at one year compared with preoperative values. Transplants showed no signs of rejection in patients who were able to continue the immunosuppressants for six months. Postoperative surgical complications included cataract progression requiring surgery (three of eight phakic eyes), retinal detachment (three eyes), intraoperative retinal breaks (two eyes), and macular pucker (two eyes). None of the patients developed cystoid macular edema on postoperative fluorescein angiography or postoperative inflammation.
A sheet of adult human allogeneic RPE can be transplanted into the subretinal space in AMD patients at the time of subfoveal membranectomy. Systemic immune suppression appeared to prevent rejection of the transplanted tissue, but did not lead to an improvement in visual function.
Maculoplasty for age-related macular degeneration: Reengineering Bruch's membrane and the human macula
2006, Progress in Retinal and Eye Research
Age-related macular degeneration (AMD) is the leading cause of blindness in the western world. Over the last decade, there have been significant advances in the management of exudative AMD with the introduction of anti-VEGF drugs; however, many patients with exudative AMD continue to lose vision and there are no effective treatments for advanced exudative AMD or geographic atrophy. Initial attempts at macular reconstruction using cellular transplantation have not been effective in reversing vision loss. Herein we discuss the current status of surgical attempts to reconstruct damaged subretinal anatomy in advanced AMD. We reinforce the concept of maculoplasty for advanced AMD, which is defined as reconstruction of macular anatomy in patients with advanced vision loss. Successful maculoplasty is a three-step process that includes replacing or repairing damaged cells (using transplantation, translocation or stimulation of autologous cell proliferation); immune suppression (if allografts are used to replace damaged cells); and reconstruction or replacement of Bruch's membrane (to restore the integrity of the substrate for proper cell attachment).
In the current article we will review the rationale for maculoplasty in advanced AMD, and discuss the results of initial clinical attempts at macular reconstruction. We will then discuss the role of Bruch's membrane damage in limiting transplant survival and visual recovery, and discuss the effects of age-related changes within human Bruch's membrane on the initial attachment and subsequent proliferation of transplanted cells. We will discuss attempts to repair Bruch's membrane by coating with extracellular matrix ligands, anatomic reconstitution of the inner collagen layer, and the effects of Bruch's membrane reconstruction of ultrastuctural anatomy and subsequent cell behavior. Lastly, we will emphasize the importance of continued efforts required for successful maculoplasty.
Retinal pigment epithelial cell transplantation after subfoveal membranectomy in age-related macular degeneration: Clinicopathologic correlation
2001, American Journal of Ophthalmology
Citation Excerpt :
Although patients with presumed ocular histoplasmosis syndrome and other disorders can experience a significant improvement in vision after submacular surgery, extension of these techniques to patients with age-related macular degeneration has not achieved similar success. Clinical and experimental evidence suggests that retinal pigment epithelium transplantation combined with subfoveal membranectomy is a logical next step in the management of subfoveal choroidal neovascularization in age-related macular degeneration.28–30,36–38 Atrophy of the subfoveal choriocapillaris is present in over 90% of age-related macular degeneration eyes after submacular surgery26 and is correlated with poor visual recovery.27
PURPOSE: To report the histopathology after retinal pigment epithelial cell transplantation and subfoveal membranectomy in age-related macular degeneration.
METHODS: An 85-year-old white woman with bilateral choroidal neovascularization underwent subfoveal membranectomy combined with transplantation of a sheet of human adult retinal pigment epithelium (retinal pigment epithelium) under the foveal center in the right eye. The patient was immunosuppressed postoperatively with prednisone, cyclosporine, and azathioprine. The patient died from congestive heart failure 114 days after surgery.
RESULTS: A patch of hyperpigmentation was visible at the transplant site under the foveola after surgery. Mound-like clusters of individual round, large densely pigmented cells were present in the subretinal space and outer retina in this area. There was loss of the photoreceptor outer segments and native retinal pigment epithelium in the center of the transplant bed, with disruption of the outer nuclear layer predominantly over regions of multilayered pigmented cells. Cystic spaces were present in the inner and outer retina. A residual intra-Bruchs membrane component of the original choroidal neovascular complex was present under the transplant site.
CONCLUSIONS: The transplant site contained clusters of round, pigmented cells that did not form a uniform monolayer in most areas. The morphology at the transplant site is consistent with the lack of visual improvement seen after surgery in this patient.
Retinal pigment epithelial debridement as a model for the pathogenesis and treatment of macular degeneration
1996, American Journal of Ophthalmology
To determine the effects of the absence of the retinal pigment epithelium on the choriocapillaris and outer retina by performing retinal pigment epithelial cell debridement with mitomycin C to inhibit cell proliferation pharmacologically in the porcine eye.
A pars plana vitrectomy was performed in 12 eyes, and two neurosensory retinal detachments per eye were created by injecting 10^–3 mg/ml mitomycin C and 0.25% edetic acid into the subretinal space. Twenty minutes later, the retinal pigment epithelium was debrided, and the retina was reattached with a fluid-gas exchange.
Bruch's membrane was devoid of native retinal pigment epithelium, and the choriocapillaris was patent immediately after debridement. No proliferation of the retinal pigment epithelium occurred 1 week after debridement, and choriocapillaris atrophy was present beneath areas of Bruch's membrane that were devoid of retinal pigment epithelium. Four weeks postsurgery, choriocapillaris atrophy persisted in all debrided blebs, although unpigmented retinal pigment epithelium repopulated portions of Bruch's membrane in one of three blebs. Outer retinal atrophy was present in areas of Bruch's membrane with no retinal pigment epithelium and no choriocapillaris 4 weeks postsurgery. The choriocapillaris was patent in areas of mitomycin C injection without debridement.
Absence of the retinal pigment epithelium leads to atrophy of the choriocapillaris within 1 week after surgery. This finding provides an animal model to study transplantation of retinal pigment epithelium onto bare patches of Bruch's membrane in age-related macular degeneration and other diseases and provides insight into the pathogenesis of nonexudative age-related macular degeneration.
Advancement in nanostructure-based tissue-engineered biomaterials for retinal degenerative diseases
2021, Biomedicines
Epigenetics in age-related macular degeneration: new discoveries and future perspectives
2020, Cellular and Molecular Life Sciences

View all citing articles on Scopus

: Presented in part at a meeting of the International Ophthalmic Microsurgical Research Group, Southampton, Bermuda, October 1992.

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Experimental and Surgical Aspects of Retinal Pigment Epithelial Cell Transplantation

Abstract

Progress in Brain Research

Exp. Eye Res.

Exp. Eye Res.

Exp. Eye Res.

Ophthalmology

Ophthalmology

Autotransplantation of cultured retinal epithelium to Bruch's membrane in the rabbit eye

Transplantation Proceedings

Transplantation of cultured human retinal epithelium to Bruch's membrane of the owl monkey's eye

Curr. Eye Res.

Transplantation of cultured human retinal cells to monkey retina

An. Acad. brasil Cienc.

Transplantation of cultured retinal epithelium

Transplantation of retinal epithelium prevents photoreceptor degeneration in the RCS rat

Transplantation of retinal epithelial cells

Invest. Ophthalmol. Vis. Sci.

Retinal pigment epithelial transplantation: technique and possible applications

Advances in the Biosciences

Transplantation of retinal pigment epithelium in the miniature pig

Invest. Ophthalmol. Vis. Sci.

Transplantation of retinal pigment epithelium using a pars plana approach

Eye