ABSTRACT
PURPOSE: This paper aims to review the morphological and functional characteristics of patients affected by familial amyloid polyneuropathy (FAP), with greater focus on type I and its progression after liver transplantation. We also analyse therapeutic options for the ophthalmic manifestations. METHODS: The literature from 2002 through 2015 was reviewed, with a total of 45 articles studied, using the key terms related to amyloidosis and its therapeutic approaches. Information was collated, evaluated, critically assessed, and then summarised in its present form. PATHOPHYSIOLOGY AND TREATMENT: FAP results from mutation of the transthyretin gene, with Val30Met being the most frequent substitution. The symptoms are those typical of a sensorimotor autonomic neuropathy and can be halted with liver transplantation. Nowadays there are new medical therapies that delay the progression of the systemic neuropathy. However, there are still no options to avoid ocular disease. CONCLUSION: The main ocular manifestations in patients with FAP type I are amyloid deposition in the vitreous, dry eye, and secondary glaucoma. Despite liver transplantation, eye synthesis of amyloid persists and is associated with progressive ocular manifestations, which require continued ophthalmologic follow-up. New therapeutic strategies are therefore needed, particularly to target the ocular synthesis of the abnormal protein.
Subject(s)
Amyloid Neuropathies, Familial , Adult , Amyloid Neuropathies, Familial/diagnosis , Amyloid Neuropathies, Familial/pathology , Amyloid Neuropathies, Familial/physiopathology , Amyloid Neuropathies, Familial/therapy , Female , Humans , Iris/pathology , Male , Middle AgedABSTRACT
Cytoplasmic male sterility is a maternally inherited trait in higher plants that prevents the production of functional pollen. Ogura cytoplasmic male sterility in radish (Raphanus sativus) is regulated by the orf138 mitochondrial locus. Male fertility can be restored when orf138 accumulation is suppressed by the nuclear Rfo locus, which consists of three genes putatively encoding highly similar pentatricopeptide repeat proteins (PPR-A, -B, and -C). We produced transgenic rapeseed (Brassica napus) plants separately expressing PPR-A and PPR-B and demonstrated that both encoded proteins accumulated preferentially in the anthers of young flower buds. Immunodetection of ORF138 showed that, unlike PPR-B, PPR-A had no effect on the synthesis of the sterility protein. Moreover, immunolocalization experiments indicated that complete elimination of ORF138 from the tapetum of anthers correlated with the restoration of fertility. Thus, the primary role of PPR-B in restoring fertility is to inhibit ORF138 synthesis in the tapetum of young anthers. In situ hybridization experiments confirmed, at the cellular level, that PPR-B has no effect on the accumulation of orf138 mRNA. Lastly, immunoprecipitation experiments demonstrated that PPR-B, but not PPR-A, is associated with the orf138 RNA in vivo, linking restoration activity with the ability to directly or indirectly interact with the orf138 RNA. Together, our data support a role for PPR-B in the translational regulation of orf138 mRNA.
Subject(s)
Plant Infertility/genetics , Plant Proteins/genetics , Plant Proteins/metabolism , Raphanus/genetics , Raphanus/metabolism , Amino Acid Sequence , Brassica rapa/genetics , Brassica rapa/metabolism , Immunoprecipitation , In Situ Hybridization , Microscopy, Fluorescence , Mitochondrial Proteins/chemistry , Mitochondrial Proteins/genetics , Mitochondrial Proteins/metabolism , Models, Genetic , Molecular Sequence Data , Plant Proteins/chemistry , Plants, Genetically Modified/genetics , Plants, Genetically Modified/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Sequence Homology, Amino AcidABSTRACT
PURPOSE: To report the results of limbal transplantation (LT) in patients with limbal stem cell deficiency (LSCD) in the context of ocular surface diseases. MATERIALS AND METHODS: A multicenter (5 centers) retrospective case series analysis of patients who underwent LT between 1996 and 2004 was performed. Data were collected by the same researcher using a customized database. Success was defined by the absence of a persistent corneal epithelial defect, on-going inflammation or recurrence of a pterygium. RESULTS: Data from 72 LT performed in 61 patients (65 eyes) with a mean follow-up of 20.8 months (SD 23.5; range, 3-115) were analyzed. There were 33 males and 28 females with a mean age of 55.8 years (SD: 15.6; range, 20-89). Fifty-eight (80.6%) LT were autografts (40 pterygia, 12 alkali burns, 3 iatrogenic cases, 2 viral infections, 1 neoplasia case) and 14 (19.4%) were allografts from cadaveric donors (7 immune-based disorders, 6 alkali burns, 1 iatrogenic case); all patients receiving allografts also received systemic immunosuppression. Of the total number of LT, 48 (66.7%) were successful. This proportion increased to 81.0% (47/58) when autografts were used. However, only 7.1% (1/14) of all allografts were successful. The success rate was higher (80.0%) when performed for a pterygium and lower when done for immune-based inflammation (14.3%). CONCLUSION: Autograft tissue for LT is always preferable to allografts to surgically treat LSCD, as clinical success is significantly higher, and systemic immunosuppression is avoided. As expected, immune-based disorders are the most difficult cases to treat. LT has been shown to be an excellent option for recurrent pterygium, although prospective studies need to be performed to further corroborate these results.
