ABSTRACT
BACKGROUND: VogtâKoyanagiâHarada (VKH) disease is a multifactorial systemic autoimmune disorder against melanocytes that is characterized by panuveitis. Familial occurrence of VKH disease is rare. Here, we report two cases of a father and his son with characteristic manifestations of VKH disease. CASE PRESENTATION: A 53-year-old male with typical clinical symptoms of VKH disease was referred to Tangshan Eye Hospital. Examination showed the presence of ciliochoroidal effusion and exudative retinal detachment in both eyes. The patient was given intravenous methylprednisolone 120 mg for 2 days and intravenous methylprednisolone 80 mg for 1 day followed by 48 mg (1 mg/kg/day) oral methylprednisolone daily, accompanied by oral azathioprine 50 mg daily. Cycloplegic agent (0.5% tropicamide three times daily [TID]) was added. The patient was free of symptoms and recurrence within more than 1-year-follow-up period, the best corrected visual acuity (BVCA) was increased and maintained in both eyes with complete resolution of subretinal fluid. One year and nine months later, case 2 (his son) also presented with the typical clinical symptoms of VKH disease at 29 years of age. The son also recovered from VKH disease after routine and standard treatment. CONCLUSIONS: To the best of our knowledge, this is the first VKH disease case report of a father-son relationship. Although genetic factors have been demonstrated to be involved in the pathogenesis of VKH disease, the different inheritance modes of VKH patients need to be further explored and studied.
Subject(s)
Glucocorticoids , Methylprednisolone , Uveomeningoencephalitic Syndrome , Humans , Male , Middle Aged , Fathers , Glucocorticoids/therapeutic use , Methylprednisolone/therapeutic use , Nuclear Family , Uveomeningoencephalitic Syndrome/diagnosis , Uveomeningoencephalitic Syndrome/drug therapy , Uveomeningoencephalitic Syndrome/complications , Adult , Visual Acuity , Treatment OutcomeABSTRACT
Accumulation of lipofuscin in the retinal pigment epithelium (RPE) is considered a major cause of RPE dysfunction and senescence in age-related macular degeneration (AMD), and N-retinylidene-N-retinylethanolamine (A2E) is the main fluorophore identified in lipofuscin from aged human eyes. Here, human-induced pluripotent stem cell (iPSC)-RPE was generated from healthy individuals to reveal proteomic changes associated with A2E-related RPE cell senescence. A novel RPE cell senescence-related protein, high-mobility group box 1 (HMGB1), was identified based on proteomic mass spectrometry measurements on iPSC-RPE with A2E treatment. Furthermore, HMGB1 upregulated Caveolin-1, which also was related RPE cell senescence. To investigate whether changes in HMGB1 and Caveolin-1 expression under A2E exposure contribute to RPE cell senescence, human ARPE-19 cells were stimulated with A2E; expression of HMGB1, Caveolin-1, tight junction proteins and senescent phenotypes were verified. HMGB1 inhibition alleviated A2E induced cell senescence. Migration of RPE cells was evaluated. Notably, A2E less than or equal to 10µM induced both HMGB1 and Caveolin-1 protein upregulation and HMGB1 translocation, while Caveolin-1 expression was downregulated when there was more than 10µM A2E. Our data indicate that A2E-induced upregulation of HMGB1ãCaveolin-1 and HMGB1 release may relate to RPE cell senescence and play a role in the pathogenesis of AMD.
