Vitreous amyloidosis after liver transplantation in patients with familialamyloid polyneuropathy: ocular synthesis of mutant transthyretin

Vitreous amyloidosis has bee reported in patients with familial amyloidotic polyneuropathy (FAP) who are carriers of different mutant transthyretins ( TTR). The mutant TTR constitutes the majority of the amyloid vitreous fibri ls in heterozygous Val30Met patients. Due to the ocular synthesis of TTR, i t is possible that the retina constitutes the source of vitreous amyloid fi brils; if so, orthotopic liver transplantation (OLT) performed to remove th e mutant TTR from circulation might not be effective in treating/avoiding v itreous amyloid. We present vitreous amyloidosis in a FAB patient from Maio rca with ATTR Val30Met who underwent OLT at age 38. Progressive impairment of visual acuity (VA) appeared bilaterally 2 years after OLT due to vitreou s opacities consistent with amyloid; successful bilateral vitrectomy was pe rformed. Amyloid was demonstrated in the vitrectomy material by Congo red s taining; immunohistochemistry and Western blotting analyses were positive w ith an antibody for human TTR. Mass spectrometry of TTR revealed the presen ce of the mutant in approximately 20% of the TTR. Future structural studies on vitreous material with different proportions of normal/versus mutant TT R might shed some light on TTR fibrillogenesis. These results show that vit reous deposition of TTR amyloid fibrils occurs after OLT, suggesting that o ngoing intraocular synthesis of mutant TTR might contribute to this process . We also present the progression after OLT of vitreous amyloidosis previou sly diagnosed in three patients with TTR Val71Ala.