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Débridement of the Pig Retinal Pigment Epithelium In Vivo FREE

Lucian V. Del Priore, MD, PhD; Russ Hornbeck; Henry J. Kaplan, MD; Zelma Jones; Tony L. Valentino, PhD; Judith Mosinger-Ogilvie, PhD; Mark Swinn
Arch Ophthalmol. 1995;113(7):939-944. doi:10.1001/archopht.1995.01100070113034
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Objective:  To study the morphologic effects of surgical débridement of the retinal pigment epithelium (RPE) in an animal model.

Methods:  A pars plana vitrectomy was performed in the domestic pig, and a neurosensory retinal detachment was created by injecting the calcium-chelating agent edetic acid (commonly referred to as ethylenediaminetetraacetic acid or EDTA) into the subretinal space through a retinotomy. Twenty minutes later, the RPE was débrided by gently brushing Bruch's membrane with a soft-tip silicone catheter. Dissociated RPE was aspirated from the subretinal space, and the retina was reattached with a fluid-gas exchange.

Results:  Light microscopic analysis confirmed that Bruch's membrane was devoid of native RPE and the choriocapillaris was morphologically intact immediately after débridement. Photoreceptor outer segments were disrupted and foreshortened immediately after RPE débridement. One to 4 weeks later, a layer of hypopigmented RPE covered most of the previously débrided areas of Bruch's membrane. The choriocapillaris was intact in areas of Bruch's membrane that were repopulated by hypopigmented RPE, and remained intact 12 weeks after débridement. Some regions of Bruch's membrane near the retinotomy remained devoid of RPE for more than 4 weeks after débridement. The choriocapillaris was atrophic and there was extensive disruption of the outer retinal layers in these areas.

Conclusions:  The RPE healed in most areas after surgical débridement of the RPE in the experimental animal. Atrophy of the choriocapillaris was present in areas of poor RPE healing near the retinotomy.

REFERENCES

Gouras P, Flood MT, Kjeldbye H, Bilek MK, Eggers H.  Transplantation of cultured human retinal epithelium to Bruch's membrane of the owl monkey's eye . Curr Eye Res . 1985;;4:253-265.
Gouras P, Flood MT, Kjeldbye H.  Transplantation of cultured human retinal cells to monkey retina . An Acad Bras Cienc . 1984;;56:431-443.
Gouras P, Lopez R, Brittis M, Kjeldbye HM, Fasano MK.  Transplantation of cultured retinal epithelium . In: Agardh E, Ehinger B, eds. Retinal Signal Systems, Degenerations and Transplants . Amsterdam, the Netherlands: Elsevier Science Publishers; 1986;:271-286.
Brittis M, Lopez R, Gouras P, Kjeldbye H.  Autotransplantation of cultured retinal epithelium to Bruch's membrane in the rabbit eye . Transplant Proc . 1987;;19:1133-1136.
Lopez R, Gouras P, Brittis M, Kjeldbye H.  Transplantation of cultured rabbit retinal epithelium to rabbit retina using a closed-eye method . Invest Ophthalmol Vis Sci . 1987;;28:1131-1137.
Gouras P, Lopez R, Kjeldbye H, Sullivan B, Brittis M.  Transplantation of retinal epithelium prevents photoreceptor degeneration in the RCS rat . In: LaVail M, Anderson RE, Hollyfield J, eds. Inherited and Environmentally Induced Retinal Degenerations . New York, NY: Alan R Liss Inc; 1989;:659-671.
Li L, Sheedlo HJ, Gaur V, Turner JE.  Effects of macrophage and retinal pigment epithelial cell transplants on photoreceptor cell rescue in RCS rats . Curr Eye Res . 1991;;10:947-958.
Li L, Sheedlo HJ, Turner JE.  Long-term rescue of photoreceptor cells in the retinas of RCS dystrophic rats by RPE transplants . Prog Brain Res . 1990;;82:179-185.
Li L, Turner JE.  Inherited retinal dystrophy in the RCS rat: prevention of photoreceptor degeneration by pigment epithelial cell transplantation . Exp Eye Res . 1988;;47:911-917.
Li L, Turner JE.  Transplantation of retinal pigment epithelial cells to immature and adult rat hosts: short- and long-term survival characteristics . Exp Eye Res . 1988;;47:771-785.
Lopez R, Gouras P, Kjeldbye H, et al.  Transplanted retinal pigment epithelium modifies the retinal degeneration in the RCS rat . Invest Ophthalmol Vis Sci . 1989;;30:586-588.
Sheedlo HJ, Li L, Turner JE.  Functional and structural characteristics of photoreceptor cells rescued in RPE-cell grafted retinas of RCS dystrophic rats . Exp Eye Res . 1989;;48:841-854.
Lane C, Boulton M.  Retinal pigment epithelial transplantation: technique and possible applications . Adv Biosci . 1987;;63:125-138.
Lane C, Boulton M, Bridgman A, Marshall J.  Transplantation of retinal pigment epithelium in the miniature pig . Invest Ophthalmol Vis Sci . 1990;;31( (suppl) ): 405.
Lane C, Boulton M, Marshall J.  Transplantation of retinal pigment epithelium using a pars plana approach . Eye . 1989;;3:27-32.
Berger AS, Kaplan HJ.  Clinical experience with the surgical removal of subfoveal neovascular membranes . Ophthalmology . 1992;;99:969-976.
Thomas MA, Kaplan HJ.  Surgical removal of subfoveal neovascularization in the presumed ocular histoplasmosis syndrome . Am J Ophthalmol . 1991;;111:1-7.
Thomas MA, Grand MG, Williams DF, Lee CM, Pesin SR, Lowe MA.  Surgical management of subfoveal choroidal neovascularization . Ophthalmology . 1992;;99:952-968.
Michels RG. Vitreous Surgery . St Louis, Mo: CV Mosby Co; 1981;.
Lagunowich LA, Grunwald GB.  Expression of calcium-dependent cell adhesion during ocular development: a biochemical, histochemical and functional analysis . Dev Biol . 1989;;135:158-171.
Del Priore LV, Hornbeck R, Kaplan HJ, Jones Z, Swinn M.  Surgical removal of the retinal pigment epithelium causes atrophy of the choriocapillaris and outer retina . Invest Ophthalmol Vis Sci . 1995;;36( (suppl) ):1142.
Whittaker JR.  Transnational competition as a possible basis of modulation in retinal pigment cell cultures . J Exp Zool . 1968;;169:143-159.
Robbins SR. Robbins Pathologic Basis of Disease . Philadelphia, Pa: WB Saunders Co; 1974;.
Beauchemin ML.  The fine structure of the pig's retina . Graefes Arch Clin Exp Ophthalmol . 1974;;190:27-45.
O'Donnell FE, Green WR.  The eye in albinism . In: Duane TD, Jaeger EA, eds. Clinical Ophthalmology . New York, NY: Harper & Row Publishers Inc; 1986;;4:15-16.
Naumann GOH, Lerche W, Schroeder W.  Foveola Aplasie bei Tyrosinase positivem oculocutaneous Albinism . Graefes Arch Clin Exp Ophthalmol . 1976;;200:39-50.
Fulton AB, Albert DM, Craft JL.  Human albinism: light and electron microscopy study . Arch Ophthalmol . 1978;;96:305-310.
Korte GE, Reppucci V, Henkind P.  RPE destruction causes choriocapillaris atrophy . Invest Ophthalmol Vis Sci . 1984;;25:1135-1145.
Henkind P, Gartner S.  The relationship between retinal pigment epithelium and the choriocapillaris . Trans Ophthalmol Soc U K . 1983;;103:444-447.
Sarks SH, Van Driel D, Maxwell L, Killingsworth M.  Softening of drusen and subfoveal neovascularization . Trans Ophthalmol Soc U K . 1980;;100:414-422.
Green WR, Key SN III.  Senile macular degeneration: a histopathologic study . Trans Am Ophthalmol Soc . 1977;;75:180-254.
Friedman E, Smith TR, Kuwabara T.  Senile choroidal vascular patterns and drusen . Arch Ophthalmol . 1963;;69:220-230.
Zarbin MA, Nasir M.  Impaired choriocapillaris perfusion following subfoveal surgery for macular degeneration . Ophthalmology . 1993;;100( (suppl) ):97.
Pollack JS, Kaplan HJ, Del Priore LV, Smith MS.  Choriocapillaris atrophy following subfoveal membrane excision in exudative age-related macular degeneration . Ophthalmology . 1993;;100( (suppl) ):122.
Nasir M, Zarbin MA.  Choriocapillaris atrophy as a complication of surgical excision of choroidal neovascular membranes . Invest Ophthalmol Vis Sci . 1993;;34( (suppl) ):834.
Pollack JS, Kaplan HJ, Del Priore LV, Smith MS.  Choriocapillaris atrophy associated with exudative age-related macular degeneration . Invest Ophthalmol Vis Sci . 1993;;34( (suppl) ):834.
Glaser BM, Campochiaro PA, Davis JL, Sato M.  Retinal pigment epithelial cells release an inhibitor of neovascularization . Arch Ophthalmol . 1985;;103:1870-1875.
Campochiaro PM, Glaser BM.  Endothelial cells release a chemoattractant for retinal pigment epithelial cells in vitro . Arch Ophthalmol . 1985;;103:1876-1880.
Glaser BM, D'Amore PA, Michels RGM, Patz A, Fenselau A.  Demonstration of vasoproliferative activity from mammalian retina . J Cell Biol . 1980;;84:298-304.
Del Monte MA, Maumenee IH.  New techniques for in vitro culture of human retinal pigment epithelium . Birth Defects . 1980;;16:327-338.
Hay ED: In: Hay ED, ed. Cell Biology of Extracellular Matrix . New York, NY: Plenum Press; 1981;:379-409.
Reh TA, Nagy T, Gretton H.  Retinal pigmented epithelial cells induced to trans-differentiate to neurons by laminin . Nature . 1987;;330:68-71.
Song M-K, Lui GM.  Propagation of fetal human RPE cells: preservation of original culture morphology after serial passage . J Cell Physiol . 1990;;143:196-203.

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Gouras P, Flood MT, Kjeldbye H, Bilek MK, Eggers H.  Transplantation of cultured human retinal epithelium to Bruch's membrane of the owl monkey's eye . Curr Eye Res . 1985;;4:253-265.
Gouras P, Flood MT, Kjeldbye H.  Transplantation of cultured human retinal cells to monkey retina . An Acad Bras Cienc . 1984;;56:431-443.
Gouras P, Lopez R, Brittis M, Kjeldbye HM, Fasano MK.  Transplantation of cultured retinal epithelium . In: Agardh E, Ehinger B, eds. Retinal Signal Systems, Degenerations and Transplants . Amsterdam, the Netherlands: Elsevier Science Publishers; 1986;:271-286.
Brittis M, Lopez R, Gouras P, Kjeldbye H.  Autotransplantation of cultured retinal epithelium to Bruch's membrane in the rabbit eye . Transplant Proc . 1987;;19:1133-1136.
Lopez R, Gouras P, Brittis M, Kjeldbye H.  Transplantation of cultured rabbit retinal epithelium to rabbit retina using a closed-eye method . Invest Ophthalmol Vis Sci . 1987;;28:1131-1137.
Gouras P, Lopez R, Kjeldbye H, Sullivan B, Brittis M.  Transplantation of retinal epithelium prevents photoreceptor degeneration in the RCS rat . In: LaVail M, Anderson RE, Hollyfield J, eds. Inherited and Environmentally Induced Retinal Degenerations . New York, NY: Alan R Liss Inc; 1989;:659-671.
Li L, Sheedlo HJ, Gaur V, Turner JE.  Effects of macrophage and retinal pigment epithelial cell transplants on photoreceptor cell rescue in RCS rats . Curr Eye Res . 1991;;10:947-958.
Li L, Sheedlo HJ, Turner JE.  Long-term rescue of photoreceptor cells in the retinas of RCS dystrophic rats by RPE transplants . Prog Brain Res . 1990;;82:179-185.
Li L, Turner JE.  Inherited retinal dystrophy in the RCS rat: prevention of photoreceptor degeneration by pigment epithelial cell transplantation . Exp Eye Res . 1988;;47:911-917.
Li L, Turner JE.  Transplantation of retinal pigment epithelial cells to immature and adult rat hosts: short- and long-term survival characteristics . Exp Eye Res . 1988;;47:771-785.
Lopez R, Gouras P, Kjeldbye H, et al.  Transplanted retinal pigment epithelium modifies the retinal degeneration in the RCS rat . Invest Ophthalmol Vis Sci . 1989;;30:586-588.
Sheedlo HJ, Li L, Turner JE.  Functional and structural characteristics of photoreceptor cells rescued in RPE-cell grafted retinas of RCS dystrophic rats . Exp Eye Res . 1989;;48:841-854.
Lane C, Boulton M.  Retinal pigment epithelial transplantation: technique and possible applications . Adv Biosci . 1987;;63:125-138.
Lane C, Boulton M, Bridgman A, Marshall J.  Transplantation of retinal pigment epithelium in the miniature pig . Invest Ophthalmol Vis Sci . 1990;;31( (suppl) ): 405.
Lane C, Boulton M, Marshall J.  Transplantation of retinal pigment epithelium using a pars plana approach . Eye . 1989;;3:27-32.
Berger AS, Kaplan HJ.  Clinical experience with the surgical removal of subfoveal neovascular membranes . Ophthalmology . 1992;;99:969-976.
Thomas MA, Kaplan HJ.  Surgical removal of subfoveal neovascularization in the presumed ocular histoplasmosis syndrome . Am J Ophthalmol . 1991;;111:1-7.
Thomas MA, Grand MG, Williams DF, Lee CM, Pesin SR, Lowe MA.  Surgical management of subfoveal choroidal neovascularization . Ophthalmology . 1992;;99:952-968.
Michels RG. Vitreous Surgery . St Louis, Mo: CV Mosby Co; 1981;.
Lagunowich LA, Grunwald GB.  Expression of calcium-dependent cell adhesion during ocular development: a biochemical, histochemical and functional analysis . Dev Biol . 1989;;135:158-171.
Del Priore LV, Hornbeck R, Kaplan HJ, Jones Z, Swinn M.  Surgical removal of the retinal pigment epithelium causes atrophy of the choriocapillaris and outer retina . Invest Ophthalmol Vis Sci . 1995;;36( (suppl) ):1142.
Whittaker JR.  Transnational competition as a possible basis of modulation in retinal pigment cell cultures . J Exp Zool . 1968;;169:143-159.
Robbins SR. Robbins Pathologic Basis of Disease . Philadelphia, Pa: WB Saunders Co; 1974;.
Beauchemin ML.  The fine structure of the pig's retina . Graefes Arch Clin Exp Ophthalmol . 1974;;190:27-45.
O'Donnell FE, Green WR.  The eye in albinism . In: Duane TD, Jaeger EA, eds. Clinical Ophthalmology . New York, NY: Harper & Row Publishers Inc; 1986;;4:15-16.
Naumann GOH, Lerche W, Schroeder W.  Foveola Aplasie bei Tyrosinase positivem oculocutaneous Albinism . Graefes Arch Clin Exp Ophthalmol . 1976;;200:39-50.
Fulton AB, Albert DM, Craft JL.  Human albinism: light and electron microscopy study . Arch Ophthalmol . 1978;;96:305-310.
Korte GE, Reppucci V, Henkind P.  RPE destruction causes choriocapillaris atrophy . Invest Ophthalmol Vis Sci . 1984;;25:1135-1145.
Henkind P, Gartner S.  The relationship between retinal pigment epithelium and the choriocapillaris . Trans Ophthalmol Soc U K . 1983;;103:444-447.
Sarks SH, Van Driel D, Maxwell L, Killingsworth M.  Softening of drusen and subfoveal neovascularization . Trans Ophthalmol Soc U K . 1980;;100:414-422.
Green WR, Key SN III.  Senile macular degeneration: a histopathologic study . Trans Am Ophthalmol Soc . 1977;;75:180-254.
Friedman E, Smith TR, Kuwabara T.  Senile choroidal vascular patterns and drusen . Arch Ophthalmol . 1963;;69:220-230.
Zarbin MA, Nasir M.  Impaired choriocapillaris perfusion following subfoveal surgery for macular degeneration . Ophthalmology . 1993;;100( (suppl) ):97.
Pollack JS, Kaplan HJ, Del Priore LV, Smith MS.  Choriocapillaris atrophy following subfoveal membrane excision in exudative age-related macular degeneration . Ophthalmology . 1993;;100( (suppl) ):122.
Nasir M, Zarbin MA.  Choriocapillaris atrophy as a complication of surgical excision of choroidal neovascular membranes . Invest Ophthalmol Vis Sci . 1993;;34( (suppl) ):834.
Pollack JS, Kaplan HJ, Del Priore LV, Smith MS.  Choriocapillaris atrophy associated with exudative age-related macular degeneration . Invest Ophthalmol Vis Sci . 1993;;34( (suppl) ):834.
Glaser BM, Campochiaro PA, Davis JL, Sato M.  Retinal pigment epithelial cells release an inhibitor of neovascularization . Arch Ophthalmol . 1985;;103:1870-1875.
Campochiaro PM, Glaser BM.  Endothelial cells release a chemoattractant for retinal pigment epithelial cells in vitro . Arch Ophthalmol . 1985;;103:1876-1880.
Glaser BM, D'Amore PA, Michels RGM, Patz A, Fenselau A.  Demonstration of vasoproliferative activity from mammalian retina . J Cell Biol . 1980;;84:298-304.
Del Monte MA, Maumenee IH.  New techniques for in vitro culture of human retinal pigment epithelium . Birth Defects . 1980;;16:327-338.
Hay ED: In: Hay ED, ed. Cell Biology of Extracellular Matrix . New York, NY: Plenum Press; 1981;:379-409.
Reh TA, Nagy T, Gretton H.  Retinal pigmented epithelial cells induced to trans-differentiate to neurons by laminin . Nature . 1987;;330:68-71.
Song M-K, Lui GM.  Propagation of fetal human RPE cells: preservation of original culture morphology after serial passage . J Cell Physiol . 1990;;143:196-203.

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