BIGH3 (TGFBI) Arg124 mutations influence the amyloid conversion of related peptides in vitro.

Amyloid deposits with Arg124 mutated TGFBI protein have been identified in autosomal dominant blinding corneal dystrophies. We assessed in vitro the mechanisms determining TGFBI protein amyloid transformation involving mutations of Arg124. Eight peptides synthesized following the TGFBI protein sequence, centered on codon Arg124 holding the previously reported amyloidogenic mutations and the respective controls were studied. Cys124 and His124 mutated peptide preparations contained significantly higher amounts of amyloid than the native peptide. Blocking the SH group of Cys124 and deleting the first four NH2-terminal amino acids including Val112-Val113 resulted in a decrease in amyloid fibril formation while deletion of the nine CONH2-terminal residues increased amyloid fibril concentration. Fourrier transformed-infrared spectroscopy analysis of the different peptide solutions showed an increase in beta-pleated sheet structures in those with enhanced amyloid yielding. We designed a peptide (BB1) likely to counteract the role of Val112-Val113 in amyloid fibril formation. Incubation of Cys124 peptide with BB1 indeed resulted in a 35% inhibition of amyloid fibril formation. Our results are in keeping with the clinical observations of Arg124 mutation-linked amyloidosis and show the importance of Val112-Val113, disulfide and hydrogen bonding in increasing the beta-pleated conformation and amyloid formation. These findings shed new light on the molecular mechanisms of TGFBI protein amyloidogenesis and encourage further research on the use of specifically designed peptides as putative therapeutic agents for these disabling diseases.

Clinical, histopathologic, and ultrastructural characteristics of BIGH3(TGFBI) amyloid corneal dystrophies are supportive of the existence of a new type of LCD: the LCDi.

PURPOSE: To assess the morphologic differences of three types of lattice corneal dystrophies (LCDs) from histologic, immunohistochemical, and ultrastructural studies. METHODS: Corneas from three patients, one LCD1, one His626Arg-LCD, and one LCD3A were processed for Congo red, betaig-h3(541-564) antibodies immunostaining, and electron transmission microscopy studies. Control tissues were submitted to identical analyses and consisted of one cornea from a patient not having LCD and one skin biopsy from the patient suffering from LCD1. RESULTS: The three corneas displayed birefringent congophilic deposits under polarized light, confirming their amyloid nature. The deposits differed regarding their shape and location in each of the corneas. A strong immunoreactivity for betaig-h3 was shown in the LCD1 and His626Arg-LCD deposits, which was faint for the LCD3A deposits. Ultrastructural analysis confirmed the dissimilarity of the deposits among the different types of LCD. No amyloid deposits were observed in the skin from the LCD1 patient, whereas immunostaining showed the presence of high amounts of betaig-h3. CONCLUSION: Our results show that betaig-h3 is involved in amyloid deposition in all the LCDs included in the study (LCD1, His626Arg-LCD, and LCD3A). These three forms of LCD, clinically different, were also distinguishable histologically, confirming that they belong to distinctive groups of LCDs. The absence of amyloid deposition in skin from the LCD1 patient supports cornea-specific amyloid formation. In light of the present clinical, histologic, and ultrastructural data, His626Arg and related LCDs constitute a separate group of LCD that could be considered as of intermediate type on clinical grounds.

Accuracy of IRAS GT interferometer and potential acuity meter prediction of visual acuity after phacoemulsification: prospective comparative study.

PURPOSE: To assess and compare the accuracy of 2 methods of predicting visual acuity after phacoemulsification. SETTING: Department of Ophthalmology, Montpellier, France. METHODS: This prospective study evaluated 47 eyes of 47 patients having uneventful phacoemulsification over a 1-month period. All the patients had mild to moderate cataract. Visual acuity recovery was predicted using the white-light IRAS GT interferometer on the 3- and 8-degree wide test area and the Guyton-Minkowski potential acuity meter (PAM). Best corrected visual acuity was evaluated 1 day before and 1 month after surgery. RESULTS: Both the interferometer and PAM underestimated the retinal visual capacity. Three-degree white-light interferometry gave significantly better mean predicted results than 8-degree interferometry and the PAM. There was no statistically significant disparity between predicted and postoperative results with 3-degree interferometry (1.04 +/- 0.57 logMAR; -0.09 +/- 0.27 decimal) (P =.0647) and a statistically significant disparity with 8-degree interferometry (0.89 +/- 0.59 logMAR; -0.13 +/- 0.27 decimal) and the PAM (0.66 +/- 0.62 logMAR; -0.22 +/- 0.24 decimal) (P =.0001). The predicted values were widely dispersed; the correlation indices were 0.38 with the PAM (P =.091), 0.39 with 3-degree interferometry (P =.001), and 0.49 with 8-degree interferometry (P =.0005). CONCLUSIONS: Three-degree white-light interferometry gave more accurate results than 8-degree interferometry and the PAM. The wide dispersion of results and unsatisfactory correlation indices show the tests are poor predictors of individual acuity. They should be used semiquantitatively and the results interpreted in relation to the clinical data. Qualitative methods may be useful in confirming or refuting visual recovery capacity ascertained by quantitative systems.