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Transplantation Epithelial Pigment Retinal Human of Status• 50chapteCurrent

Figure 50.1  Retinal pigment epithelium (RPE) suspension transplant in exudative age-related macular degeneration (AMD). A patient with a preoperative vision of 0.05 at 2 m (ETDRS) and a large choroidal neovascularization due to AMD received a suspension of autologous RPE harvested in the nasal periphery. One month postoperatively, her vision remained stable at 0.06 at 2 m (ETDRS).

laser irradiation. Postoperative function was demonstrated with microperimetry, which showed stable fixation and maintained retinal sensitivity over the transplant.

Overall, a mean decline of visual loss is reported if postoperative complications are included. If these cases are excluded from visual analysis, the mean gain in visual acuity is 2–3 lines.2 Van Meurs’ group underscored the latter correlation in a prospective statistical analysis of 48 cases.20 As long as the complication rates remain high, the possible gain of vision limits this surgical technique to cases otherwise not treatable with pharmacologic treatments.24 It is therefore encouraging that mere mechanical ablation, analogous to Holz’s technique, by Ma and associates was able to demonstrate low PVR rates (14.3%) at 1-year follow-up and good functional outcomes in hemorrhagic AMD patients.25

TISSUE ENGINEERING AND RPE REPLACEMENT STRATEGIES

PROSTHESIS OR TISSUE ENGINEERING OF BRUCH’S MEMBRANE

Cellular replacement strategies of the RPE could be beneficial to patients with AMD or related diseases, but may not be effective if BM has been damaged by disease, age, and/or surgery. Delivery and long-term survival of these transplants may require a biocompatible substrate that patches or entirely replaces diseased BM.

346

Surgery and Pharmacotherapy • 5 section

Figure 50.2  Retinal pigment epithelium (RPE)/choroid patch transplant in exudative age-related macular degeneration. A patient with extensive extrafoveal subretinal fibrosis and an active neovascular lesion with a preoperative vision of 0.28 at 2 m (ETDRS) received a subfoveal autologous patch transplant of RPE/choroid. Postoperative vision was 0.08 at 4 m (ETDRS); the fluorescent angiography leakage was no longer seen.

In contrast to animal experiments,26 in vitro data suggested that freshly harvested or cultured RPE cell suspensions may fail to survive or function on a damaged BM.27 While histopathologic studies have demonstrated integration of cultured cell suspensions in the subretinal space in animals, formation of multilayered clumps that damaged the overlying neural retina has been reported. Moreover, delivery of cell suspensions to epithelially denuded BM using the bleb techni­ que often showed uneven distribution, with most of the cells settling in the periphery of the RPE lesion. Thus restoration of a continous monolayer using a cell suspension in the subretinal space appears challenging.

Many groups have tried to develop a RPE carrier substrate, which at the same time would serve as either a temporary or a permanent BM prosthesis. Having such an arrangement enables delivery of an intact epithelial patch that is simultaneously protected from hostile influences of aged BM.

Various biologic and artificial substrates have been proposed to date (Table 50.1 and Figure 50.3). Details of particular approaches are beyond the scope of this article and the interested reader is referred to Binder et al.3 Nevertheless, some unifying technical considerations are given. Perhaps the foremost criterion for a carrier material is maintenance of a clinically relevant epithelial phenotype, both in vitro and subsequently

347

348

chapteCurrent50•StatusofHumanRetinalPigmentEpithelialTransplantation

Table 50.1  List of proposed retinal pigment epithelium (RPE) transplantation carrier substrates

 

 

 

 

 

 

 

 

Literature reference

 

Material

 

RPE phenotype*

 

Thickness

 

Permeability/

 

Biodegradable

 

Surgical

 

Tissue

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

pore size

 

 

 

handling

 

reaction

Bhatt 199439

 

Cross-linked collagen

 

Poor

 

NA

 

Poor

 

No

 

Good

 

Retinal

 

 

 

 

 

 

 

 

 

 

 

 

 

 

atrophy

Bhatt 199439

 

Noncross-linked collagen

 

Good

 

10 m

 

NA

 

Yes

 

Good

 

Tolerated

Thomson 199640

 

Poly-l-lactic acid (PLLA)

 

Good

 

12 m

 

No

 

Yes

 

Good

 

Retinal

Hadlock 199941

 

 

 

 

 

 

 

 

 

 

 

 

 

damage?

Thomson 199640

 

Poly-dl-lactic-co-glycolic acid

 

Good

 

3–12 m

 

No

 

Yes

 

Good

 

Retinal

Hadlock 199941

 

(PLLA)

 

 

 

 

 

 

 

 

 

 

 

damage?

Thumann 199742

 

Descemet’s membrane

 

Good

 

10–12 m

 

Permeable

 

Maybe

 

NA

 

NA

 

 

 

 

 

 

in adults

 

 

 

 

 

 

 

 

Ho 199743

 

Gelatin

 

In situ, no culturing

 

NA

 

NA

 

Yes

 

Good

 

NA

Oganesian 199944

 

Fibrinogen

 

Good

 

NA

 

NA

 

Yes

 

Good

 

Tolerated

Farrokh Siar 199945

 

Cryoprecipitate

 

Good

 

NA

 

NA

 

Yes

 

NA

 

NA

Hartmann 199946; Nicolini 200047;

 

Lens capsule

 

Good

 

15 m

 

Not permeable (in

 

Maybe

 

Good

 

Retinal

Lee 200248;

 

 

 

 

 

 

 

native state)

 

 

 

 

 

damage

Turowski 200449

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Singh 200150

 

Hydrogel

 

Good

 

25 m

 

Permeable

 

No

 

NA

 

NA

Tezel 200251

 

Cadaveric Bruch’s membrane

 

NA

 

2–4 m

 

Permeable

 

Partially

 

Good

 

NA

Leng et al. 200352

 

Bucky carbon paper

 

Supports cell line

 

NA

 

Permeable

 

No

 

Good

 

Tolerated

Tezcaner 200353

 

Poly(hydroxybutyrate-co-

 

Supports cell line

 

5–10 m

 

NA

 

Yes

 

NA

 

NA

 

 

hydroxyvalerate) or PHBV8 film

 

 

 

 

 

 

 

 

 

 

 

 

Capeans 200354;

 

De-epithelialized amniotic

 

Good

 

100 m

 

Limited permeability

 

Yes

 

Challenging

 

Retinal

Stanzel 200555;

 

membrane

 

 

 

 

 

due to long diffusion

 

 

 

 

 

atrophy

Ohno-Matsui 200556;

 

 

 

 

 

 

 

distance

 

 

 

 

 

 

Singhal 200557

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Yeung 200458

 

Collagen gel

 

Supports cell line

 

NA

 

Permeable

 

Yes

 

Feasible

 

NA

Yellachich 200459

 

Cellulose acetate

 

Good (IPE)

 

25 m

 

100 kDa

 

No

 

Good

 

Tolerance

Lombardi 200560; Molnar 200561

 

Polycarbonate

 

Good for fetal, poor for

 

10 m

 

0.4 m

 

No

 

Good

 

Unclear

 

 

 

 

aged hRPE

 

 

 

 

 

 

 

 

 

 

Williams 200562

 

Polyurethane

 

Supports cell line

 

102–103 m

 

Not permeable

 

No

 

Good

 

NA

Stanzel 200663

 

Polyester

 

Good for fetal, poor for

 

10 m

 

0.4 m

 

No

 

Good

 

Tolerance

 

 

 

 

aged hRPE

 

 

 

 

 

 

 

 

 

 

Lu 200764

 

Collagen films

 

Supports cell line

 

2.4 m

 

Tested for 71.2 kDa

 

NA

 

 

 

NA

Stanzel 200765

 

Polyamide electrospun nanofibers

 

Good support for fetal

 

1 m

 

Permeable

 

No

 

NA

 

Tolerance

 

 

 

 

and aged hRPE

 

 

 

 

 

 

 

 

 

 

Thumann 200966

 

Collagen foil

 

Supports cell line

 

10 m

 

Permeable

 

Yes

 

Good

 

Tolerance

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

*Note that many studies listed are confounded by the use of either cell lines or animal-derived RPE cells, which may differ in culture behavior to primary human RPE.

IPE, iris pigment epithelium; hRPE, human retinal pigment epithelium.