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1.
Ann Plast Surg ; 90(5): 415-418, 2023 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-37146308

RESUMO

PURPOSE: Standard techniques for the treatment of congenital lower eyelid entropion may not yield suitable outcomes or may result in overcorrection if disinsertion of the lower eyelid retractors is not the primary cause. Herein, we propose and evaluate a technique using subciliary rotating sutures combined with a modified Hotz procedure for repair of lower eyelid congenital entropion that addresses these concerns. METHODS: A retrospective chart review was conducted of all patients who underwent lower eyelid congenital entropion repair by a single surgeon using subciliary rotating sutures combined with a modified Hotz procedure between 2016 and 2020. Study variables included patient demographics, follow-up period, postoperative complications, operative success, and recurrence. RESULTS: Twelve patients (19 eyelids) met the study inclusion criteria. The mean patient age was 7.1 ± 6.1 years (range, 0.2-22 years). Nine of the patients were female (75%) and 3 were male (25%). The distribution of eyelids was 8 right (42%) and 11 left (58%). The mean follow-up time was 19.5 ± 15 (range 2.5-45) months. There were two eyelids (11%) that had entropion recurrence after initial repair in patients with concomitant compound disease processes. Repeated repair resulted in success with no recurrence at last follow-up. Overall, the described entropion repair technique was successful and without recurrence in 17 eyelids (89%). There were no cases of ectropion, lid retraction, or other complications. CONCLUSIONS: Subciliary rotating sutures combined with a modified Hotz procedure are effective for correction of congenital lower eyelid entropion. As the technique does not manipulate the posterior layer of the lower eyelid retractors, it may be useful for when retractor reinsertion does not yield adequate improvement and may also reduce the risk of eyelid retraction and overcorrection in particular cases.


Assuntos
Entrópio , Humanos , Masculino , Feminino , Lactente , Pré-Escolar , Criança , Adolescente , Adulto Jovem , Adulto , Entrópio/cirurgia , Entrópio/congênito , Estudos Retrospectivos , Procedimentos Cirúrgicos Oftalmológicos , Pálpebras/cirurgia , Suturas , Técnicas de Sutura , Seguimentos , Resultado do Tratamento
2.
Exp Eye Res ; 215: 108899, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34929159

RESUMO

Sorsby Fundus Dystrophy (SFD) is a rare form of macular degeneration that is clinically similar to age-related macular degeneration (AMD), and a histologic hallmark of SFD is a thick layer of extracellular deposits beneath the retinal pigment epithelium (RPE). Previous studies of SFD patient-induced pluripotent stem cell (iPSC) derived RPE differ as to whether these cultures recapitulate this key clinical feature by forming increased drusenoid deposits. The primary purpose of this study is to examine whether SFD patient-derived iPSC-RPE form basal deposits similar to what is found in affected family member SFD globes and to determine whether SFD iPSC RPE may be more oxidatively stressed. We performed a careful comparison of iPSC RPE from three control individuals, multiple iPSC clones from two SFD patients' iPSC RPE, and post-mortem eyes of affected SFD family members. We also examined the effect of CRISPR-Cas9 gene correction of the S204C TIMP3 mutation on RPE phenotype. Finally, targeted metabolomics with liquid chromatography and mass spectrometry analysis and stable isotope-labeled metabolite analysis were performed to determine whether SFD RPE are more oxidatively stressed. We found that SFD iPSC-RPE formed significantly more sub-RPE deposits (∼6-90 µm in height) compared to control RPE at 8 weeks. These deposits were similar in composition to the thick layer of sub-RPE deposits found in SFD family member globes by immunofluorescence staining and TEM imaging. S204C TIMP3 correction by CRISPR-Cas9 gene editing in SFD iPSC RPE cells resulted in significantly reduced basal laminar and sub-RPE calcium deposits. We detected a ∼18-fold increase in TIMP3 accumulation in the extracellular matrix (ECM) of SFD RPE, and targeted metabolomics showed that intracellular 4-hydroxyproline, a major breakdown product of collagen, is significantly elevated in SFD RPE, suggesting increased ECM turnover. Finally, SFD RPE cells have decreased intracellular reduced glutathione and were found to be more vulnerable to oxidative stress. Our findings suggest that elements of SFD pathology can be demonstrated in culture which may lead to insights into disease mechanisms.


Assuntos
Células-Tronco Pluripotentes Induzidas , Degeneração Macular , Matriz Extracelular/metabolismo , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Degeneração Macular/metabolismo , Epitélio Pigmentado da Retina/metabolismo
3.
Transl Vis Sci Technol ; 6(3): 4, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28516002

RESUMO

PURPOSE: Previous studies have demonstrated the ability of retinal cells derived from human embryonic stem cells (hESCs) to survive, integrate into the host retina, and mediate light responses in murine mouse models. Our aim is to determine whether these cells can also survive and integrate into the retina of a nonhuman primate, Saimiri sciureus, following transplantation into the subretinal space. METHODS: hESCs were differentiated toward retinal neuronal fates using our previously published technique and cultured for 60 to 70 days. Differentiated cells were further treated with 20 µM N-[N-(3,5-Difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT) for a period of 5 days immediately prior to subretinal transplantation. Differentiated cells were labeled with a lentivirus expressing GFP. One million cells (10,000 cells/µL) were injected into the submacular space into a squirrel monkey eye, using an ab externo technique. RESULTS: RetCam imaging demonstrated the presence and survival of human donor cells 3 months after transplantation in the S. sciureus eye. Injected cells consolidated in the temporal macula. GFP+ axonal projections were observed to emanate from the central consolidation of cells at 1 month, with some projecting into the optic nerve by 3 months after transplantation. CONCLUSIONS: Human ES cell-derived retinal neurons injected into the submacular space of a squirrel monkey survive at least 3 months postinjection without immunosuppression. Some donor cells appeared to integrate into the host inner retina, and numerous donor axonal projections were noted throughout, with some projecting into the optic nerve. TRANSLATIONAL RELEVANCE: These data illustrate the feasibility of hESC-derived retinal cell replacement in the nonhuman primate eye.

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