To provide a comprehensive review of the types of amyloidosis that can be associated with ocular involvement, the images and clinical descriptions of patients with amyloidosis structurally related to gelsolin, keratoepithelin and lactoferrin were obtained in collaborations with the ophthalmology departments of hospitals in Mainz (Germany) and Helsinki (Finland).<b>Results</b>: Overall, ocular morbidity was detected in 41 of the 178 patients with amyloidosis (23%).
We analysed elastic fibre pathology in dermal and vascular tissue and plasma samples from 35 patients with AGelamyloidosis and 40 control subjects by transmission electron microscopy, immunohistochemistry and ELISA methods.
In the disease familial amyloidosis, Finnish type (FAF), also known as AGelamyloidosis (AGel), the mechanism by which point mutations in the calcium-regulated actin-severing protein gelsolin lead to furin cleavage is not understood in the intact protein.
<b>Methods:</b> Paraffin-embedded tissue sections from 25 autopsied individuals (age at death 44.4-88.6 years) with AGel amyloidosis were stained with HE, Congo red and Herovici stains and immunohistochemistry against the low molecular weight gelsolin fraction was performed.
We report the first known case of a patient who had amyloidosis both due to a mutant transthyretin (p.Val122Ile) and due to a novel variant in the gelsolin gene (p.Ala578Pro).
Mutations (D187N/Y) in the second domain of gelsolin trigger the proteolytic pathway producing amyloidogenic fragments that form the pathological hallmark of gelsolinamyloidosis and lattice corneal dystrophy type 2 (LCD2).
We conclude that a nanobody-based gene therapy using adeno-associated viruses shows great potential as a novel strategy in gelsolinamyloidosis and potentially other amyloid diseases.
The type of amyloidosis was AL in 51 patients (55.4%), non-V30M mutant ATTR in 10 (10.9%), V30M mutant ATTR in 8 (8.7%), serum amyloid A-derived amyloidosis (AA) in 6 (6.5%), wild-type ATTR in 4 (4.3%), gelsolin in 3 (3.3%), and unclassified in 10 (10.9%).
Follow-up of these cases might give us more insight into pathogenicity and potential treatment strategy of this atypical presentation of gelsolinamyloidosis.
The gelsolin gene defect causes expression of variant gelsolin, followed by systemic deposition of gelsolinamyloid (AGel) in HGA patients and even other consequences on the metabolism and function of gelsolin.