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


CONCLUSIONS
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.
Schmitt-Bernard
Clair-Florent
CF
Institut de Génétique Humaine, CNRS UPR 1142, Antigone Ophtalmologie, 141 Rue de la Cardonille, 34396 Montpellier Cedex 5, France. cfsb@mnet.fr
Schneider
Christelle
C
Argilés
Angel
A
D000368:Aged; D000682:Amyloid / Q000378:metabolism*; D000686:Amyloidosis / Q000378:metabolism / Q000473:pathology*; D003224:Congo Red; D003315:Cornea / Q000378:metabolism / Q000648:ultrastructure*; D003317:Corneal Dystrophies, Hereditary / Q000378:metabolism* / Q000473:pathology*; D016326:Extracellular Matrix Proteins; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D013194:Staining and Labeling / Q000379:methods; D016212:Transforming Growth Factor beta / Q000378:metabolism; D000099222:betaIG-H3 Protein
D000682:Amyloid; D003224:Congo Red; D016326:Extracellular Matrix Proteins; D009363:Neoplasm Proteins; D016212:Transforming Growth Factor beta; D000099222:betaIG-H3 Protein