RESUMEN
BACKGROUND AND OBJECTIVE: To assess therapies for cystoid macular edema (CME) following pars plana vitrectomy for proliferative vitreoretinopathy (PVR). PATIENTS AND METHODS: Retrospective analysis of 42 eyes developing CME after PVR surgery. Treatments included topical therapy, sub-Tenon's triamcinolone acetonide (STTA), intravitreal bevacizumab and combinations thereof. Best-corrected visual acuity (BCVA) as well as central subfield thickness (CST) were tracked. RESULTS: Mean Snellen BCVA improved from 20/598 to 20/297 (logMAR change -0.21; confidence interval [CI], -0.39 to -0.03; P = .03). Mean CST improved from 448 µm to 260 µm (CI, -248.70 to -126.06; P < 0.01). There was no difference in efficacy between treatment subgroups (analysis of variance, P = 0.16, 0.43), but STTA yielded statistically significant improvement in both categories (CI, -0.79 to -0.11; P = 0.01; and CI, -333.74 to 166.51; P < .01). CONCLUSIONS: Treatment of CME following PVR surgery is possible with a variety of different options. STTA appears to yield anatomical and visual improvement. [Ophthalmic Surg Lasers Imaging Retina. 2020;51:436-443.].
Asunto(s)
Bevacizumab/administración & dosificación , Manejo de la Enfermedad , Edema Macular/terapia , Triamcinolona Acetonida/administración & dosificación , Agudeza Visual , Vitrectomía/efectos adversos , Vitreorretinopatía Proliferativa/cirugía , Anciano , Inhibidores de la Angiogénesis/administración & dosificación , Femenino , Estudios de Seguimiento , Glucocorticoides/administración & dosificación , Humanos , Inyecciones Intravítreas , Edema Macular/diagnóstico , Edema Macular/etiología , Masculino , Receptores de Factores de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Estudios Retrospectivos , Tomografía de Coherencia Óptica , Resultado del TratamientoRESUMEN
Testosterone is necessary for the development of male pattern baldness, known as androgenetic alopecia (AGA); yet, the mechanisms for decreased hair growth in this disorder are unclear. We show that prostaglandin D(2) synthase (PTGDS) is elevated at the mRNA and protein levels in bald scalp compared to haired scalp of men with AGA. The product of PTGDS enzyme activity, prostaglandin D(2) (PGD(2)), is similarly elevated in bald scalp. During normal follicle cycling in mice, Ptgds and PGD(2) levels increase immediately preceding the regression phase, suggesting an inhibitory effect on hair growth. We show that PGD(2) inhibits hair growth in explanted human hair follicles and when applied topically to mice. Hair growth inhibition requires the PGD(2) receptor G protein (heterotrimeric guanine nucleotide)-coupled receptor 44 (GPR44), but not the PGD(2) receptor 1 (PTGDR). Furthermore, we find that a transgenic mouse, K14-Ptgs2, which targets prostaglandin-endoperoxide synthase 2 expression to the skin, demonstrates elevated levels of PGD(2) in the skin and develops alopecia, follicular miniaturization, and sebaceous gland hyperplasia, which are all hallmarks of human AGA. These results define PGD(2) as an inhibitor of hair growth in AGA and suggest the PGD(2)-GPR44 pathway as a potential target for treatment.
Asunto(s)
Alopecia/metabolismo , Cabello/efectos de los fármacos , Cabello/crecimiento & desarrollo , Prostaglandina D2/metabolismo , Cuero Cabelludo/metabolismo , Alopecia/enzimología , Animales , Epidermis/efectos de los fármacos , Epidermis/enzimología , Femenino , Perfilación de la Expresión Génica , Cabello/enzimología , Folículo Piloso/efectos de los fármacos , Folículo Piloso/crecimiento & desarrollo , Folículo Piloso/metabolismo , Humanos , Queratinocitos/efectos de los fármacos , Queratinocitos/enzimología , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Prostaglandina D2/análogos & derivados , Prostaglandina D2/análisis , Prostaglandina D2/farmacología , Prostaglandina-Endoperóxido Sintasas/metabolismo , Receptores Inmunológicos/metabolismo , Receptores de Prostaglandina/metabolismo , Cuero Cabelludo/efectos de los fármacos , Cuero Cabelludo/enzimologíaRESUMEN
We observed the structure of collagen fibrils in rat tail tendons after treatment with NKISK and cathepsin G. NKISK is a pentapeptide that has been previously shown to bind fibronectin, while cathepsin G is a serine protease that cleaves fibronectin but not type I collagen. In tendons treated with NKISK, fibrils were seen to extensively dissociate into smaller-diameter subfibrils. These subfibrils were homogeneous in diameter with an average diameter of 26.3 ± 5.8 nm. Similar, although less extensive, dissociation into subfibrils was found in tendons treated with cathepsin G. The average diameter of these subfibrils was 24.8 ± 4.9 nm. The ability of NKISK and cathepsin G to release subfibrils at physiological pH without harsh denaturants may enhance the study of the subfibrillar structure of collagen fibrils.
Asunto(s)
Catepsina G/farmacología , Colágeno/ultraestructura , Oligopéptidos/farmacología , Tendones/ultraestructura , Animales , Catepsina G/administración & dosificación , Colágeno/efectos de los fármacos , Leucocitos/enzimología , Microscopía Electrónica de Rastreo/métodos , Oligopéptidos/administración & dosificación , Ratas , Ratas Sprague-Dawley , Cola (estructura animal)/fisiología , Tendones/metabolismo , Tendones/fisiologíaRESUMEN
Androgenetic alopecia (AGA), also known as common baldness, is characterized by a marked decrease in hair follicle size, which could be related to the loss of hair follicle stem or progenitor cells. To test this hypothesis, we analyzed bald and non-bald scalp from AGA individuals for the presence of hair follicle stem and progenitor cells. Cells expressing cytokeratin15 (KRT15), CD200, CD34, and integrin, α6 (ITGA6) were quantitated via flow cytometry. High levels of KRT15 expression correlated with stem cell properties of small cell size and quiescence. These KRT15(hi) stem cells were maintained in bald scalp samples. However, CD200(hi)ITGA6(hi) and CD34(hi) cell populations--which both possessed a progenitor phenotype, in that they localized closely to the stem cell-rich bulge area but were larger and more proliferative than the KRT15(hi) stem cells--were markedly diminished. In functional assays, analogous CD200(hi)Itga6(hi) cells from murine hair follicles were multipotent and generated new hair follicles in skin reconstitution assays. These findings support the notion that a defect in conversion of hair follicle stem cells to progenitor cells plays a role in the pathogenesis of AGA.