Biochemical characterization of vitreous and cardiac amyloid in Ile84Ser transthyretin amyloidosis.

Plasma transthyretin (TTR) is synthesized in the liver and is the source for visceral amyloid deposits in TTR amyloidosis. However, TTR is also synthesized in the retinal pigment epithelium of the eye and choroid plexus of the brain. It has been postulated that vitreous amyloid, which is associated with approximately 20% of the known amyloidogenic TTR mutations, results from local synthesis of TTR in the eye. In order to elucidate if differences in amyloid between organs exists, we have analyzed vitreous and cardiac amyloid fibrils in Ile84Ser TTR patients for comparison. Analysis of guanidine hydrochloride solubilized protein from isolated vitreous and cardiac amyloid fibrils indicated that the amyloid TTR in both organs is highly proteolyzed with minor amounts of intact TTR present. While vitreous protein was amenable to direct Edman sequence analysis, cardiac protein gave low yields indicating it was mostly N-terminally blocked or inaccessible to Edman degradation. While vitreous contained major 11 kDa and minor 9 kDa fragments, cardiac contained at least three major fragments of 7-11 kDa. Vitreous protein was cleaved between Lys48-Thr49, while cardiac protein was cleaved at multiple sites in the residue 46-52 region. While deposits in both tissues were enriched in variant TTR, vitreous fibrils contained more variant protein than cardiac fibrils (80-89% vs. 60-65% Ser84TTR). These differences suggest that the mechanism or pathway of fibril formation may differ in various tissues.

Electrophysiologic findings after intravitreal bevacizumab (Avastin) treatment.

PURPOSE: To evaluate the short-term electrophysiologic effects of intravitreal bevacizumab in the treatment of exudative age-related macular degeneration (AMD). METHODS: Nine subjects with AMD who received treatment with intravitreal bevacizumab for exudative AMD underwent pretreatment testing with multifocal electroretinography (mf-ERG) or Ganzfeld electroretinography (G-ERG). All five G-ERG subjects underwent repeated testing at 1 week after intravitreal bevacizumab. All four mf-ERG subjects and four of the five G-ERG subjects underwent repeated testing with the same pretreatment protocol at 1 month after treatment. One G-ERG subject also received a second intravitreal injection of bevacizumab at 6 weeks after initial treatment and underwent repeated testing at 1 month after the second dose (3 months after initial treatment). RESULTS: All four subjects undergoing mf-ERG had improvement of the macular response at 1 month of after treatment. The average improvement in response density of the central 15 degrees of macular response was 35% (range, 11-65%). Subjects undergoing G-ERG testing had no significant changes in electrophysiologic response, although some variation in amplitude and implicit time was noted at different testing times. Optical coherence tomography central subfield thickness decreased from 298 microm at baseline to 274 microm at 1 month after treatment. Visual acuity improved in a majority of subjects. CONCLUSION: In this study, the intravitreal use of bevacizumab resulted in improvement of mf-ERG macular function responses and relatively stable G-ERG responses. The macular electrophysiologic response suggests that macular function improves with treatment. G-ERG suggests that there is no significant measurable photoreceptor toxicity with the use of intravitreal bevacizumab over the short term.