Amyloid β_1–43 Accumulates in the Lens Epithelium of Cortical Opacification in Japanese Patients

Abstract

PURPOSE.We investigated the accumulation of amyloid b (Ab 1-40 , Ab 1-42 , Ab ) in the lens epithelium of patients with opacification of five different types (cortical cataract [COR]; nuclear cataract [NUC]; posterior subcapsular cataract [PSC]; retrodots [RD]; and water clefts [WC]).METHODS. Samples were collected from Japanese patients taken during cataract surgery; Ab levels and mRNA expression were determined by ELISA and a real-time RT-PCR method, respectively.RESULTS. Levels of Ab 1-40 and Ab 1-42 in the lens epithelium of patients with COR, NUC, PSC, RD, and WC showed no significant differences in comparison with transparent lens epithelium. Levels of Ab 1-43 in the lens epithelium of patients with PSC and WC were not detected, and NUC and RD were slightly elevated. In contrast to the results in these cataract types, high Ab 1-43 levels were observed in the lens epithelium of patients with COR, and a close relationship was observed between Ab 1-43 levels and the degree of lens opacification (R ¼ 0.8229, n ¼ 6). The levels of Ab 1-43 were also higher in the lens epithelium of patients with mixed-cataract showing cortical opacification, and the Ab 1-43 levels in the lens epithelium of mixed-cataract patients with cortical opacification was significantly higher than in that of mixed-cataract patients without cortical opacification. In addition, the level of an amyloid precursor protein mRNA in the lens epithelium of mixed-cataract patients with cortical opacification was significantly higher than in transparent lens and mixed-cataract patients without cortical opacification. CONCLUSIONS.We found high levels of Ab 1-43 accumulation in the lens epithelium of Japanese patients with cortical opacification.Keywords: amyloid b, cortical cataract, human, lens epithelium, Japanese A ge-related cataracts are the most common cause of vision loss in the elderly, and the principal cause of blindness in the world. Age-related cataracts are classified by the location of the opacity within the lens: cortical cataracts (COR); nuclear cataracts (NUC); and posterior subcapsular cataracts (PSC). In addition, retrodots (RD) and water clefts (WC) have been found to be associated with visual impairment. Cataracts represent a complex disease with numerous genetic and environmental contributing factors, including smoking, ultraviolet irradiation, diabetes, the cumulative effect of X-rays, nutrition, vitamin C deficiency, hypertension, and alterations in both endocrine and enzymatic equilibria.1-8 On the other hand, it has recently been reported that the accumulation of amyloid b (Ab) peptides in the human lens may be related to the onset of lens opacification, 9-11 but this involvement in terms of etiology and Ab levels is not fully understood. 12 The enzymes a-secretase (a disintegrin and metalloproteinase, ADAM10) 13-15 ; b-secretase (b site APP cleaving enzyme, called BACE1) 16 ; and c-secretase (a presenilin complex, PS1 and PS2) 17 are known to be related to Ab production by cleaving an amyloid precursor protein (APP). The...

Enhancement of Amyloid β1–43 Production in the Lens Epithelium of Japanese Type 2 Diabetic Patients

“…In addition, we show that the enhanced Aβ 1-43 ratio may be related to the onset and/or acceleration of diabetic cataracts. These findings support our previous studies [14][15][16], and may be useful in developing therapies for diabetic cataracts.…”

“…The expressions of β-secretase and γ-secretase in mammalian lenses have been observed [11,12], and the accumulation of Aβ 1-40 and Aβ 1-42 has been reported in the cytosol of lens fiber cells from people with Alzheimer's disease [13]. We also reported that Aβ accumulates in the lens epithelium of humans with cortical opacification (senile cataracts) [14], and showed that the accumulation of Aβ in the lens accelerates lens opacification via nitric oxide-Aβ positive feedback [15]. Thus, these previous reports suggest that the accumulation of Aβ will be related to the onset of senile cataracts in studies using human lens samples.…”

“…On the other hand, it is important to investigate Aβ accumulation in the lenses of diabetic patients with cortical opacification, since the above findings were obtained from mixed-cataracts without cortical opacification. We measured Aβ 1-43 levels in the lens epithelium of diabetic patients with cortical opacification in this study (cortical opacification 2.0 ± 0.7, NUC 0.8 ± 0.8, PSC 0.5 ± 1.0, RD 1.0 ± 1.2, WC 1.3 ± 1.2, age 74.8 ± 8.6, n = 6, Male 1, Female 5), and the Aβ 1-43 levels (Aβ 1-43 , 2.9 ± 1.1 pmol/g protein, Aβ 1-43 /total-Aβ 21.5 ± 7.1 × 10 −2 ) were higher than in mixed-cataracts without cortical opacification (Aβ 1-43 , 1.83 ± 1.8 pmol/g protein, Aβ 1-43 /total-Aβ 8.8 ± 1.2 × 10 −2 ) [14]. These results show that hyperglycemia may also accelerate cortical opacification in diabetic patients.…”

“…In a previous study to measure Aβ production and accumulation in human lenses, we showed that the production and accumulation of Aβ are similar between normal patients (transparent lenses) and opaque lenses from cataract patients with NUC, PSC, RD and/or WC. However, Aβ accumulation was enhanced in the lens epithelium of humans with cortical cataracts [14]. Based on these findings, we used the lens epithelium from patients with NUC, PSC, RD and/or WC as opaque lenses (mixed-cataracts without cortical opacification).…”