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Biomedical subjects

M del Cerro

Publications and source records attributed to M del Cerro.

At least 19 recordsLinked to original sources
PubMed2001

Posterior segment approach for subretinal transplantation or injection in the canine model.

A posterior segment approach for cell transplantation or injection into the subretinal space of the dog has been developed. Controlled penetration to the subretinal space was achieved using a 29-gauge injection cannula, either blunted or with a 30 degrees sharpened bevel, and partially ensheathed with moveable plastic tubing. Depending on the injection volume used, the retina detached, and the fluid was reabsorbed within 1-3 weeks, although for smaller volumes the retina reattached within a matter of days. The optimal injection volume used was between 100 and 150 microl, or two injections of 55 microl each. By ophthalmoscopy following the surgery, it was possible to serially monitor the injection site and retinal bleb through fundus photography. Light microscopy demonstrates the distribution of stable, viable RPE cells in the subretinal space up to 6 months. The transplantation technique developed for the dog is atraumatic and free from any major surgical or clinical complications. It can be readily used to deliver cells or fluids to localized regions of the subretinal space.

Animals↗
PubMed2000

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.

Adult↗
PubMed2000

Histologic correlation of human neural retinal transplantation.

PURPOSE: To describe the histologic findings of the transplanted eye of a 94-year-old man with neovascular age-related macular degeneration, who 3 years earlier underwent subretinal transplantation of both a fetal neural retinal sheet and a retinal microaggregrate suspension. METHODS: Serial sections of the posterior segment of the eye and the transplanted areas were processed and studied by routine histologic techniques, including both light and transmission electron microscopy (TEM). Transplanted areas were also examined for the presence of glial, neuronal, and photoreceptor cell markers by standard immunohistochemical methods. RESULTS: After transplantation in this patient, there was no visual improvement. Light microscopic examination disclosed survival of the transplanted cells in the subretinal space with no evidence of inflammation or rejection. The neural retinal sheet transplant developed a layered configuration. The retinal pigment epithelium (RPE) was absent over much of the posterior pole, including the area of transplantation. TEM examination and immunohistochemical analysis disclosed the presence of neuronal and glial cells within the transplant. A few transplant neuronal cell processes overlying a focus of residual RPE cells were positive for S-antigen, but well-developed photoreceptor outer segments were not present. CONCLUSIONS: Long-term survival of transplanted neural retinal tissue can be achieved in human patients without immunosuppression. The lack of photoreceptor development in this patient may be the result of absent or dysfunctional RPE. Nonetheless, the long-term survival of grafted tissue in the human subretinal space in the absence of immunosuppressive treatment is promising for future efforts in the field of neural retinal transplantation.

Aged↗
PubMed1999

The transplantation of human fetal neuroretinal cells in advanced retinitis pigmentosa patients: results of a long-term safety study.

The purpose of this study was to determine the long-term safety of transplanting human fetal neuroretinal cells (14 to 18 week gestational age) into a series of patients with advanced retinitis pigmentosa (RP). After obtaining informed consent, both hosts and mothers of donors were screened for transmissible diseases. Pre- and postoperative clinical exams, visual acuity, electroretinograms, and fluorescein angiograms were performed and visual field testing was attempted in each case. Surgically, an anterior approach through pars plana ciliaris was used. A retinotomy was performed in the paramacular area and a two-function cannula was introduced into the subretinal space to deliver a suspension of donor cells. The cell suspension carried approximately 4000 cells/microl; the volume injected did not exceed 150 microl. The patients were examined for periods ranging from 12 to 40 months posttransplantation. To date, no evidence of inflammation, infection, or overt rejection of the graft was noted in the host eye, neither was any change observed in the contralateral, unoperated eye. In conclusion, neuroretinal cells were injected into the subretinal space of 14 patients with advanced RP with no clinical appearance of detrimental effects at the time of surgery or up to 40 months postinjection except in 1 patient who developed retinal detachment. This sets the stage for a phase II clinical trial to determine the possible beneficial effects of this procedure in patients blinded by degenerative retinal disease.

Adult↗
PubMed1998

Correlates of photoreceptor rescue by transplantation of human fetal RPE in the RCS rat.

This study uses a water maze paradigm as a tool to assess posttransplantation changes in behavior associated with a visual stimulus. A set of dystrophic RCS rats received bilateral injections of freshly isolated human fetal RPE cells into the subretinal space of the superior equatorial hemisphere. Five age-matched control dystrophic RCS rats received subretinal injections of vehicle. All animals were immunosuppressed. At 2 months posttransplantation, each rat was tested in the water escape apparatus. The rat used a single light source, randomly located on the edge of the tank, to locate a submerged platform, placed directly in front of the light. Each rat was timed and videotaped during 10 consecutive trials. The swimming paths and times for all rats were recorded and statistically analyzed. Subsequent to the water escape trials, the eyes were embedded for histologic analysis which included quantitative assessment of photoreceptor cells in predefined retinal regions. The water escape data indicated the differences between the sham and experimental groups changed significantly over time (P = 0.0017). Over time, the transplanted animals learned to use light as a clue (P < 0.0001), whereas the sham animals did not (P = 0.73). Transplanted eyes had a significantly greater mean number of photoreceptors in the superior, grafted region than seen in the inferior region of the same eyes and compared with either region of sham-injected eyes (P = 0.0023). Statistical analyses demonstrated a functional advantage for visually guided behavior in RCS rats transplanted with human fetal RPE cells and a statistically significant PRC rescue effect at 2 months after transplantation.

Animals↗
PubMed1998

A behavioral study of temporal processing and visual persistence in young and aged rats.

Young rats were presented with light flash prepulses varying in duration from 1 to 128 ms, with light offset or light onset fixed at 70 ms prior to an acoustic startle stimulus (Experiment 1A), and, with single or paired 1-ms flashes, the 2nd (or only) flash given 100 to 500 ms before the startle, and 1 ms to 400 ms interflash intervals (Experiment 1B). Older rats (10 and 20 months old) received the same single and double flashes but with the maximum interflash interval extended to 1,500 ms (Experiment 2). Reflex inhibition increased with increased duration from 1 to 8 ms and decreased as light onset progressively exceeded 100 ms. Inhibition for both single and double flashes also declined for onset lead times beyond 100 ms, then increased for a double flash once the interflash interval exceeded 100 ms in young and middle-aged rats and 1,500 ms in the oldest rats. Peak inhibition was much reduced in the oldest rats at short lead times but was greater than that of younger rats at long lead times. These data suggest that aged rats process visual stimuli more slowly than younger rats and show poorer temporal acuity coupled with greater visual persistence.

Acoustic Stimulation↗
PubMed1998

Changes in visually guided behavior of Royal College of Surgeons rats as a function of age: a histologic, morphometric, and functional study.

PURPOSE: To compare the changes in visually guided performance as a function of age between Royal College of Surgeons (RCS) dystrophic and congenic rats and to correlate photoreceptor cell number with visually guided performance in age-matched populations of RCS dystrophic rats. METHODS: The visually guided performances of RCS dystrophic (n=6) and congenic (n=7) rats were studied from 0.75 to 12 months of age using a water escape paradigm that tested their ability to find a submersed, randomly placed platform that used a light source as a clue. The time to find the platform (latency) was recorded. In age-matched dystrophic RCS rats, histopathologic changes were described and the number of photoreceptor cell nuclear profiles per midsagittal retinal section was counted. Changes with age in visually guided behavior and photoreceptor cell populations of RCS dystrophic rats then were compared. RESULTS: The latency of RCS dystrophic rats increased significantly beyond that of congenic rats after 6 months of age. Photoreceptor cell number in dystrophic rats precipitously decreased through 6 months of age, stabilized at 9 months, and decreased further at 12 months. Two unexpected results were seen in the dystrophic animals: At 6 months of age, as few as 22+/-3 photoreceptor cell nuclei per midsagittal section provided similar latencies as at 2 months when there were as many as 400. Although the number of photoreceptor cells remained stable from 6 to 9 months of age, functional vision significantly deteriorated. CONCLUSIONS: Two important phenomena were observed. First, the RCS rats performed very well in the water escape test even while their photoreceptor cell population was being decimated. Second, once a low threshold was reached, a dramatic deterioration of visually guided behavior occurred without a further reduction in photoreceptor cell numbers.

Aging↗
PubMed1997

The first decade of continuous progress in retinal transplantation.

In recent months, neural fetal retina has been transplanted into blind human patients affected by Retinitis Pigmentosa. Initial success, as documented by improved visual activity, has been reported (del Cerro et al., Neuroscience Abstract, 1996). With the rapid progress in human patients, additional questions are arising concerning transplantation issues. Additional answers and further success in treating clinical disease will necessarily come from new laboratory research in animal models as well as in vitro systems. This increases the need for evaluation of the data already gathered over the first decade of retinal transplantation. The extensive experimental background work that preceded the current wave of human retinal transplants is reviewed in this paper, with particular emphasis given to the work dealing with the transplantation of neural retina.

Animals↗
PubMed1997

Efficacy of nonfetal human RPE for photoreceptor rescue: a study in dystrophic RCS rats.

This study determines the efficacy of nonfetal human retinal pigment epithelium (RPE) for photoreceptor rescue utilizing the dystrophic RCS rat as an animal model. Eyes from 10- and 49-year-old donors were obtained through the Rochester Eye and Human Parts Bank. The RPE was isolated by enzymatic treatment of the choroid-RPE with 2% dispase for 30 min at 37 degrees C. Mechanically dissociated RPE cells were injected at the superior hemisphere into the subretinal space of dystrophic RCS rats during the fourth postnatal week. Rats receiving vehicle injection served as sham controls. The animals were immunosuppressed with daily cyclosporine injections (10 mg/kg) and sacrificed 30 days posttransplantation for histologic evaluation of the RPE graft and its effect on photoreceptor survival. Transplantation of adult human RPE promoted the survival of photoreceptors in the dystrophic RCS rat. Morphometric analysis of the grafted superior hemisphere demonstrated a threefold increase in photoreceptor cell density (149.2 +/- 50 SD) compared to sham controls (39.7 +/- 31 SD) and the untouched inferior hemisphere (52.8 +/- 28 SD). RPE from the 49-year-old donor was as effective as RPE from the 10-year-old donor in promoting photoreceptor survival. The results of this study in RCS rats suggests that RPE from adult human donors of varied ages is suitable for transplantation and retains the capability to promote survival of photoreceptor cells. This finding opens the possibility of using nonfetal RPE cells in human retinal transplantation.

Aged↗
PubMed1997

Posterior capsule polishing with the neodymium:YLF picosecond laser: model eye study.

PURPOSE: To determine the ability and threshold energy of the neodymium:yttrium-lithium-fluoride (Nd:YLF) picosecond laser to achieve micron-level polishing of a latex posterior capsule facsimile (PCF) as an alternative to laser capsulotomy to treat posterior capsule opacification. SETTING: University of Rochester Medical Center, Rochester, New York, USA. METHODS: A solid-state, mode-locked Nd:YLF picosecond laser was used to polish a latex PCF in contact with a poly(methyl methacrylate) intraocular lens (IOL) in an experimental model eye. Eight study groups were treated at different energy levels ranging from 5 to 15 microJ. All treatments were done at least three times in different latex capsules and lenses. An atomic force microscope was used to measure IOL damage and an interferometric surface analysis microscope to assess the polishing effect on the PCF. The IOLs were further subjected to a scatter analysis to assess the optical significance of the damage produced. RESULTS: The latex PCF revealed a polishing effect with all energy settings used. The IOLs were damaged with all energy settings but 5 microJ. Energy settings higher than 5 microJ caused significantly more polishing effect to the latex and damage to the lenses. At the 10 microJ energy level, a single parameter with no depth produced a relative polishing depth of 3.01 microns +/- 0.10 (root mean square +/- SD). At this energy, the damage to the IOLs was 188 +/- 20.52 nm, and it was associated with typical craters over the surface at regular intervals that corresponded to each individual laser pulse. CONCLUSION: This model documented the feasibility of achieving micron-level precision in excising material with the picosecond laser and showed that posterior capsule polishing should be feasible and safe in human eyes.

Humans↗
PubMed1997

Fluorescein as a marker for subretinal transplantation of human fetal neural retina.

PURPOSE: To investigate the effect of fluorescein on human fetal neural retina and adult rat retina; and to use fluorescein to map the area of subretinal transplantation. METHODS: In vitro: Human fetal neural retina (8 to 14 weeks gestational age) was incubated in 0.03% fluorescein in Dulbecco's Modified Eagles Medium (DMEM) or DMEM alone for 30 min. Viability was determined using the trypan blue exclusion test, and results were compared. Effects of the fluorescein on cell morphology were assessed by observation of primary cultures for 1 week. In vivo: Human fetal neural retina was mechanically dissociated in 0.03% fluorescein in DMEM and transplanted to the subretinal space of immunosuppressed rats. To control for the effect of fluorescein on the grafted tissue, transplants were also performed in DMEM only. After transplantation, indirect ophthalmoscopy and true color fundus photography were performed to document the area covered by the transplant. One month after transplantation, the appearance of grafts exposed to fluorescein was compared to those that were not, at the light microscopic level. RESULTS: In vitro: Exposure of human fetal neural retina to fluorescein had no effect on viability. Similarly, in tissue culture, the fluorescein-exposed cells exhibited the same phenotype as the controls. In vivo: Immediately after transplantation the graft site was clearly outlined within the subretinal area and fluoresced intensely. There were no traces of the dye 2 h after transplantation. Cells that were transplanted with fluorescein survived transplantation, and one month after transplantation could be seen forming subretinal grafts. No differences were noted between these and control grafts. CONCLUSIONS: Fluorescein is an effective dye for immediate and transient localization of trans-scleral transplants to the subretinal space. It allows mapping of the area covered by the injection without interfering with the viability and differentiation of the transplanted cells. It allows unequivocal photo- and video-documentation in both the albino and pigmented fundi. It is already FDA approved for many other extra- and intraocular studies and now has directly been shown to be non-toxic to both human fetal neural retina and adult rodent retina.

Animals↗
PubMed1996

Water escape performance of adult RCS dystrophic and congenic rats: a functional and histomorphometric study.

The dystrophic Royal College of Surgeons (RCS) rat undergoes photoreceptor degeneration due to a hereditary defect in the retinal pigment epithelium. The congenic rat remains unaffected. Although the retinal degeneration is well characterized, few functional studies of this strain are available. We wished to compare the visual function of congenic and dystrophic RCS rats using a water escape paradigm that tested their ability to find a submersed, randomly placed platform using a light source as a clue. Three different behavioral experiments were sequentially performed on all animals: Experiment 1--The Light and Platform test measured the time to swim from the center of the pool to a platform located under a light clue. Each animal was given 10 trials. Experiment 2--The No Light with Platform test was performed as above except no light clue was used. Experiment 3--The Light and No Platform test was performed with a light clue but without a platform. The animal was allowed to swim for 2 min. All trials were videotaped. After the final experiment, the animals were sacrificed and a histomorphometric analysis of their retinas were performed. Expt. 1--The time to find the platform using light as a clue was greater for the dystrophic than for the congenic rats. Expt. 2--In the absence of light clue, there was no significant difference in performance between the congenic and dystrophic animals. Expt. 3--In the absence of a platform, a significantly greater amount of time was spent in the area indicated by the light clue by the congenic animals as compared to the dystrophic. Morphometric analysis revealed a mean number of 133 photoreceptor nuclear profiles/90 microns of retina for congenic rats as compared to 0.14 for dystrophic rats. This simplified version of the Morris water maze permits quantitative evaluation of visually-guided behavior in an important model of retinal degeneration.

Animals↗
PubMed1996

Cyclosporine treatment promotes survival of human fetal neural retina transplanted to the subretinal space of the light-damaged Fischer 344 rat.

We have reported that xenografts of human fetal neural retina survive in the subretinal space of cyclosporine-immunosuppressed rats. In view of the current controversy regarding the role of cyclosporine, we wished to determine if cyclosporine immunosuppression was an absolute requirement for retinal xenograft survival. Neural retinas from human fetal eyes obtained within 1 h of termination of pregnancy were stored in Optisol medium (Chiron Vision, Irvine, CA) at 4 degrees C for 2 and 7 days. Retinas were then transplanted to the subretinal space of either cyclosporine-treated (10 mg/kg/day) light-damaged Fischer 344 rat eyes (17 animals, 28 eyes) or to the subretinal space of light-damaged Fischer 344 rat eyes (9 animals, 15 eyes) receiving no cyclosporine treatment. Grafted eyes were observed clinically at 10, 20, and 30 days posttransplantation. At 30 days, the animals were sacrificed and the grafts observed histologically. Human fetal retina xenografted to the subretinal space of immunosuppressed rats survived (9/17 animals, 12/28 eyes), showed good integration with the host retina and initial photoreceptor differentiation. Tissue xenografted to the subretinal space of non-cyclosporine-treated rats was not observed to survive (0/9 animals, 0/15 eyes). A low level cellular reaction was seen around three of the injection sites within the nonimmunosuppressed rats. We conclude that immunosuppression is necessary for the survival of human fetal neural retina xenografted to the subretinal space.

Animals↗
PubMed1996

Infundibulocystic basaloid neoplasm.

Infundibulocystic basal cell carcinoma was described in 1987 as a new type of basal cell carcinoma with follicular differentiation. A great controversy followed this description, mainly about the malignant or benign character of this neoplasm and the distinction from other tumors with follicular differentiation. We present two new cases of this neoplasm: the first one had the typical features of this entity, except for the absence of stroma; the second one showed in the deep portion basaloid nodules similar to those of a nodular basal cell carcinoma. We review the criteria adduced to establish the malignant character of this neoplasm and conclude that both the nosology and biological behavior of this neoplasm with follicular differentiation remain to be determined.

Aged↗
PubMed1996

Transplantation of human fetal retinal pigment epithelium rescues photoreceptor cells from degeneration in the Royal College of Surgeons rat retina.

PURPOSE: The Royal College of Surgeons (RCS) rat suffers from a well-characterized, early-onset, and relentless form of photoreceptor cell degeneration. It has been shown that allografts of retinal pigment epithelial cells from normal perinatal rats have rescue effects in this condition. In preparation for human application, the authors determined whether human fetal retinal pigment epithelium (RPE) grafts have a photoreceptor rescue effect in RCS dystrophic rat retinas. METHODS: Sheets of RPE from human fetal eyes (10 to 16 weeks gestational age) were isolated according to the authors' recently described method. Fragments of the RPE sheets were transplanted to the subretinal space within the superior hemisphere. Transplants were performed within the superior equatorial region of five dystrophic RCS rats, one eye per animal. A similar volume of vehicle was injected into the subretinal space of five age-matched control rats, again one eye per rat. All rats were immunosuppressed with daily injections of cyclosporine. Using light microscopy, photoreceptor cell nuclear profiles of superior equatorial (SE) and inferior equatorial (IE) regions of transplanted and sham-injected control animals were counted. RESULTS: Four weeks after transplantation, a dramatic rescue effect was observed. Microscopically, presumptive donor RPE cells were seen as single pigmented cells and as cell clusters in the subretinal space. An outer nuclear layer three to four profiles thick was present in the area of the RPE transplant but was nearly absent in the rest of the retina, as well as in the retinas of control rats. The number of photoreceptor nuclear profiles per 100 microns was 34.7 +/- 2.2 (mean +/- SEM) in the SE region of transplanted rats and 3.5 +/- 1.4 in the same region of sham-injected rats. There were 3.0 +/- 1.0 photoreceptor nuclear profiles in the IE region of transplanted rats and 3.5 +/- 1.2 in the IE region of sham-injected eyes. No evidence of graft rejection was seen. CONCLUSIONS: This study provides the first indication that transplanted human fetal RPE cells are able to rescue photoreceptor cells in a model of hereditary retinal degeneration.

Animals↗
PubMed1996

Corneal incisions utilizing the 1,053-nm picosecond Nd:YLF ophthalmic laser.

We evaluated the precision and predictability of a 1,053-nm picosecond Nd:YLF ophthalmic laser with various combinations of computer-controlled parameters. We utilized epithelium-free corneal-sclera preparations from NZW rabbits, and the 1,053-nm Nd:YLF laser (Intelligent Surgical Lasers, San Diego, CA, U.S.A.). X-line and line patterns were utilized to make linear corneal incisions. Three parameters (layer size, crossing width, and energy level) were evaluated. One parameter was changed for a total of 120 combinations of computer-controlled parameters. Three incisions were performed for each combination. Although the intended depths of the incisions were constant (300 mu m), the actual depths of the incisions varied with the change of parameters. Increasing layer size decreased the depth of incisions, and increasing crossing width or energy level increased the depth of incisions. Only three of 120 combinations of parameters achieved depths near 300 mu m. Within the same combination of parameters, the depth of the corneal incisions varied. Debris of ablated stromal tissue was observed at the border and partially occupying the incision. Most of the incisions were "funnel"-shaped with the distal treatment zone having a "zigzag" or irregular border. Further improvements are necessary to use this laser system for corneal transverse incisions.

Animals↗