Challenges faced by older people with dementia during the COVID-19 pandemic as perceived by professionals: a qualitative study with interviews.

BACKGROUND: Previous studies have highlighted a decline in the mental health of older adults over the course of the coronavirus disease 2019 (COVID-19) pandemic. Few studies have determined the possible causes of behavioural and psychological symptoms of dementia during COVID-19 in a comprehensive manner. We aimed to identify the challenges faced by older adults with dementia during the COVID-19 pandemic. METHODS: This study adopted a qualitative approach to understanding the perceptions of healthcare professionals, such as regarding the negative effects of COVID-19 on the mental health of people with dementia. Between January and March 2022, the authors conducted individual in-depth interviews on how COVID-19 affected the stress levels, care, and self-determination of people with dementia. Qualitative data from the individual interviews were data cleansed to ensure the clarity and readability of the transcripts. The qualitative data were then analyzed by inductive manual coding using a qualitative content analysis approach. The grouping process involved reading and comparing individual labels to cluster similar labels into categories and inductively formulate themes. RESULTS: Qualitative analysis extracted 61 different semantic units that were duplicated. Seven categories were inductively extracted using a grouping process. These were further integrated to extract the following four themes: fear of personal protective equipment (PPE), loneliness, dissatisfaction with behavioural restrictions and limitations of video calls, and family interference with service use. DISCUSSION: People with dementia often faced mental distress during the pandemic owing to preventive measures against COVID-19, and a lack of awareness and understanding of such preventive measures worsened their distress. They experienced a severe sense of social isolation and loneliness. Findings also indicated that families tended to ignore the needs of people with dementia and their decisions and opinions regarding healthcare service use.

Microfabrication of Gelatin Methacrylate/Hydroxyapatite Composites by Utilizing Alternate Soaking Process.

To construct a complex three-dimensional (3D) structure mimicking bone microstructure, hydrogel models of polymerized gelatin methacrylate (pGelMA) were fabricated by using stereolithography and modified with hydroxyapatite (HAp) via an alternate soaking process (ASP) using a solution of calcium and phosphate ions. Fabricated pGelMA line models whose widths were designed as 100, 300, and 600 µm were modified with HAp by ASP by changing the immersion time and number of cycles. After ASP, all of the line models with widths of 100, 300, and 600 µm were successfully modified with HAp, and large amounts of HAp were covered with the fabricated models by increasing both the immersion time and the number of cycles in ASP. HAp was observed near the surface of the line model with a width of 600 µm after ASP at an immersion time of 10 s, while the entire model was modified with HAp using ASPs for longer immersion times. The adhesion and spread of mesenchymal stem cells (MSCs) on the pGelMA-HAp discs depended on the ASP conditions. Moreover, the HAp modification of 3D pyramid models without alteration of the microstructure was also conducted. This two-step fabrication method of first fabricating frameworks of hydrogel models by stereolithography and subsequently modifying the fabricated models with HAp will lead to the development of 3D cell culture systems to support bone grafts or to create biological niches, such as artificial bone marrow.

Association between hearing status and social participation in Japanese older adults: A cross-sectional study from the Japan gerontological evaluation study.

PURPOSE: Hearing is known to decline with age. As sensitivity to speech declines, conversation becomes more difficult and social interactions are affected, resulting in increased risk of cognitive decline. This study aimed to examine the relationship between hearing status and social participation. MATERIALS AND METHODS: The study included 21,117 adults aged 65 years or older who responded to a survey in 2019. The survey asked participants about their hearing status and how frequently they participated in certain social activities. RESULTS: The analysis of the relationship between degree of hearing and social activity showed lower hearing status odds ratios for those who participated more frequently in social activities compared to those who participated less frequently. The odds ratios were as follows, hobby clubs (OR 0.81, 95%CI 0.78-0.84), activities such as teaching skills or passing on experiences to others (OR 0.69, 95%CI 0.65-0.75), and meeting with friends (OR 0.77, 95%CI 0.74-0.79). Compared to those who did not participate in social activities, those who participated in three or more types of groups had significantly lower hearing impairment (OR 0.75, 95% CI 0.72-0.79). CONCLUSION: Hearing impairment was shown to inhibit participation in activities, including those that require communication with multiple people or smooth communication, those that involve a wide range of ages, and those that involve work and movement. Hearing impairment should be identified and addressed in its early stages to prevent its negative impact on social participation.

Oral function and cumulative long-term care costs among older Japanese adults: a prospective 6-year follow-up study of long care receipt data.

OBJECTIVES: This study evaluated the relationship between status of oral function and related long-term care service costs. DESIGN: This was a prospective 6-year follow-up study of previous survey data. SETTING: The data were obtained from the Japan Gerontological Evaluation Study conducted between 2010 and 2011. PARTICIPANTS: The participants were functionally independent older adults in 12 municipalities across Japan. INTERVENTIONS: Care service benefit costs were tracked over 6 years using publicly available claims records (n=46 616) to monitor respondents' cumulative care costs. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome variable was the cumulative cost of long-term care insurance services during the follow-up period. We adjusted for the presence or absence of oral function problems, age, sex, physical function and socioeconomic and lifestyle background at the time of the baseline survey. RESULTS: Tobit analysis revealed that, compared with those with no oral function problems, cumulative long-term care service benefit costs for those with one, two or three oral function problems were approximately US$4020, US$4775 and US$82 92, respectively, over 6 years. Compared with those with maintained oral function, there was a maximum difference of approximately US$8292 in long-term care service costs for those with oral function problems. With increase in number of oral function problems, there was a concomitant elevation in the cost of long-term care. CONCLUSIONS: Oral function in older people was associated with cumulative long-term care insurance costs. The oral function of older people should be maintained to reduce future accumulated long-term care insurance costs. Compared with those with maintained oral function, there was a maximum difference of approximately US$8292 in long-term care service costs for those with oral function problems. The cost of long-term care was amplified as oral problems increased.

Self-reported hearing and vision impairment and incident frailty in Japanese older people: A 3-year longitudinal analysis of the Japan Gerontological Evaluation Study.

BACKGROUND: We examined the associations and interactions of hearing impairment (HI) and vision impairment (VI) with frailty. METHODS: We performed a 3-year longitudinal analysis of the Japan Gerontological Evaluation Study (JAGES), a nationwide prospective cohort study of functionally independent Japanese older people (age ≥ 65 years). Frailty status at baseline and follow-up was defined according to the Kihon Checklist. HI and VI at baseline were self-reported. Logistic regression models were used to examine the main and interaction effects of HI and VI on incident frailty during a 3-year follow-up period. RESULTS: Of the 7,852 participants (mean age 73.2 years, standard deviation 5.6; 50.7% women), 9.7%, 5.3%, and 1.9% reported HI, VI, and concurrent HI and VI, respectively. After adjusting for possible confounders and the other sensory impairment, VI (odds ratio [OR] 2.50, 95% confidence interval [CI] 1.62-3.85, p < 0.001), but not HI (OR 1.29, 95% CI 0.97-1.72, p = 0.081), was significantly associated with incident combined pre-frailty and frailty from a robust baseline. No interaction was observed between HI and VI (OR 0.83, 95% CI 0.38-1.81, p = 0.636). We observed no significant associations between sensory impairments and incident frailty from a pre-frail baseline (HI: OR 1.26, 95% CI 0.88-1.80, p = 0.205; VI: OR 1.44, 95% CI 0.90-2.31, p = 0.127; interaction between HI and VI: OR 1.16, 95% CI 0.53-2.53, p = 0.718). CONCLUSIONS: VI, rather than HI, may be an independent risk factor for frailty, without any interaction between the two.

Association between Social Activity and Development of Dementia in Hearing Impairment: A Cohort Study in Japan from Japan Gerontological Evaluation Study.

We aimed to clarify the association between social activity and the development of dementia in older adults by hearing-impaired (HI) status. We applied a community-based prospective cohort study over 6 years as part of the Japan Gerontological Evaluation Study. The study included 53,549 participants aged 65 years and older who did not require long-term care. A baseline questionnaire survey was conducted; explanatory variables included physical and social activities, and the objective variable was dementia onset assessed by standardized protocol. Cox regression models were used to calculate hazard ratios (HRs) for dementia stratified by HI status. During the follow-up period, 6013 (11.2%) participants developed dementia. Analyses revealed increased dementia risk for participants with HI who participated in the following activities less than once a month: sport groups (HR 2.17, 95% CI 1.53-3.08), hobby groups (HR 1.70, 95% CI 1.34-2.17), going out (HR 2.19, 95% CI 1.51-3.17), and meeting with friends (HR 1.27, 95% CI 1.06-1.53). HI and lack of social activity increase the risk of dementia. The study results indicate that there is an association between low social activity and the development of dementia in people with HI; the strongest associations were found for low participation in sports and hobby groups.

Hemodialysis patients with coronavirus disease 2019: reduced antibody response.

BACKGROUND: Because patients on maintenance hemodialysis (HD) have an impaired immune response to pathogens, they are at higher risk of severe coronavirus disease 2019 (COVID-19). However, data on antibody production among HD patients with COVID-19 is scarce. Thus, we performed a retrospective cohort study evaluating severe acute respiratory syndrome coronavirus two antibody (SARS-CoV-2) production within 1 month after COVID-19 onset in hospitalized patients on HD. METHODS: SARS-CoV-2-specific immunoglobulin (Ig) G levels were quantified using an iFlash 3000 Chemiluminescence Immunoassay analyzer (Shenzhen YHLO Biotech Co., Ltd.) to detect IgG antibodies specific for the S1 subunit of the spike protein (IgG-S1). Propensity score matching was used to balance covariate distribution in HD and non-HD patients. From April 2020 to February 2021, antibody testing was performed on 161 hospitalized patients with symptomatic COVID-19. Of them, 34 HD patients were matched to 68 non-HD patients. RESULTS: After propensity score matching, the median levels of IgG-S1 in the HD patients at 7-13 days after symptom onset were significantly lower than in non-HD patients, especially in those with severe disease. Among all patients, those with severe disease produced lower levels of IgG-S1 at 7-13 days compared with non-severe patients. CONCLUSION: COVID-19 patients with severe disease, especially those undergoing HD, had lower IgG-S1 production in the second week of the disease. Thus, the increased risk of severe COVID-19 in HD patients may be, in part, due to a slow and reduced antibody response.

Association between Food Store Availability and the Incidence of Functional Disability among Community-Dwelling Older Adults: Results from the Japanese Gerontological Evaluation Cohort Study.

This study sought to clarify the association between food store availability and the incidence of disability in older adults. This study utilized a population-based cohort study of independent Japanese adults aged ≥65 years, which was a 6 year follow-up of participants in the Japan Gerontological Evaluation Study. A total of 31,273 respondents were extracted. Food store availability was evaluated based on the existence of food stores within 500/1000 m of the home. We utilized participant-reported subjective measurement as well as geographic information system-based objective measurement for the evaluation. The incidence of disability was determined using municipal data on eligibility for long-term care insurance benefits. There were 7643 (24.4%) community-dwelling participants with low subjective food store availability and 5673 (18.1%) with low objective food store availability. During the follow-up period of 6 years, the cumulative incidence of disability was 20.9%, with a significant association between low subjective food store availability and increased disability. Participants who reported low subjective food store availability had a significantly higher likelihood of developing disability (hazard ratio = 1.18, 95% confidence interval: 1.11-1.25) than those who reported high subjective food store availability after adjusting for age, sex, sociodemographic status, environmental status, walking and going out, dietary food intake, body mass index, and comorbidities. Low subjective food store availability was associated with early onset of disability. Accessibility of food stores might contribute to maintaining a disability-free life.

Radiofrequency catheter ablation for inappropriate sinus tachycardia in a patient with systemic lupus erythematosus: a case report.

BACKGROUND: Systemic lupus erythematosus (SLE) is known to cause inappropriate sinus tachycardia (IST). However, there is limited evidence available with regard to the treatment of IST in this setting. In this article, we report a case of drug refractory IST in a patient with SLE treated with radiofrequency catheter ablation (RFCA) using a non-contact mapping system. CASE SUMMARY: A 33-year-old woman had been diagnosed with SLE in 2001. She presented with complaints of persistent palpitations for 1 month and persistent sinus tachycardia. She underwent RFCA using a non-contact mapping system for drug refractory IST. The voltage and activation maps did not show obvious differences in the earliest activation site at heart rates (HRs) 90-150 b.p.m. In contrast, the areas of breakout sites were clearly distinguished between those from the normal P-wave zones at HR <140 b.p.m. and those from higher rate sites at HR >140 b.p.m. Radiofrequency catheter ablation was performed in those areas as the target for ablation. Thereafter, the symptoms steadily disappeared and the maximum HR-using 24-h Holter monitoring-decreased from 156 to 120 b.p.m. DISCUSSION: Radiofrequency catheter ablation using a non-contact mapping system was applied to the treatment of drug refractory IST in a patient with SLE. Of note, IST in such patients may be left untreated. This approach may be considered as a first-line therapy option for drug refractory IST in patients with SLE.

[Problems of Home-Visiting Speech-Language-Hearing Therapists in Dysphagia Management].

There are fewer reports by speech-language-hearing therapists than those by physical therapists or occupational therapists for visiting rehabilitation. Therefore, we examined the present situation with emphasis on professional roles of speech-language- hearing therapists working in visiting rehabilitation, patient tendency, and dysphagia rehabilitation. A questionnaire survey and interview survey were conducted on 6 speech-language-hearing therapists working in visiting rehabilitation. In the questionnaire, personal attributes, subject area, details of dysphagia rehabilitation, professional duties, and tendency of patient in charge were collected. In the interview survey, we asked about trends and request status, evaluation and training protocol for patients with dysphagia, activities related to pneumonia prevention, and future directions in the field. Results show that many linguistichearing experts worked with dysphagia patients, indicating that the needs for respiratory rehabilitation and dysphagia rehabilitation are high. In this survey, the environment surrounding visiting speech-language-hearing therapists and patients with dysphagia was clarified.

Successful treatment with steroid and cyclosporine A in a patient with immunoglobulin A-proliferative glomerulonephritis with monoclonal immunoglobulin deposits.

We report a case of glomerulonephritis with monoclonal immunoglobulin (Ig) A deposits as a form of monoclonal gammopathy of renal significance (MGRS) caused by monoclonal immunoglobulins without blood disorders in a 41-year-old woman. She developed lower leg oedema and was hospitalized because of nephrotic syndrome. Serum and urine were negative for M protein, and the free light chain κ/λ ratio was within the normal range. Renal histopathological findings included mesangial proliferation, endocapillary cell proliferation, and a double-contour appearance of the capillary walls. Immunofluorescent staining indicated IgA and C3 deposits on the mesangium and capillary walls. Only λ chain and IgA1 deposits were noted. Fine granular sub-endothelial deposits with no specific structure were observed under electron microscopy. The patient was diagnosed with IgA-proliferative glomerulonephritis with monoclonal immunoglobulin deposits (IgA-PGNMID). The patient had decreased urine protein and sediment erythrocytes after she underwent two rounds of steroid pulse therapy and oral steroid therapy, but proteinuria and haematuria still remained. Four months later, the patient was administered 50 mg/day cyclosporine (CsA), and proteinuria and haematuria dramatically decreased. Only a few case reports have been published on IgA-PGNMID. This case is rare in that the patient achieved successful treatment using a combination of steroids and CsA.

Axonal Protection by Ripasudil, a Rho Kinase Inhibitor, via Modulating Autophagy in TNF-Induced Optic Nerve Degeneration.

Purpose: The Rho kinase inhibitor ripasudil decreases intraocular pressure, although its role in optic nerve axonal damage should be clarified. We therefore investigated whether ripasudil modulates TNF-induced axonal loss and affects autophagy machinery after the induction of optic nerve degeneration. Methods: Rats were given intravitreal injection of TNF, concomitant injection of ripasudil hydrochloride hydrate and TNF, or ripasudil alone. Axon numbers were counted to evaluate the effects of ripasudil against axon loss. Immunoblot analysis was performed to examine p62 as well as LC3-II expression in optic nerves. Electron microscopy was used to determine autophagosome numbers in axons and glia. Immunogold labeling was performed to evaluate autophagosomes in axons. Results: Ripasudil injected intravitreally resulted in significant neuroprotection against TNF-induced axon loss. Intravitreal TNF injection upregulated p62 in the optic nerve, but ripasudil completely inhibited this increment. The ripasudil alone injection diminished p62 and enhanced LC3-II protein levels significantly compared with baseline. Ripasudil-induced upregulation of LC3-II was seen after TNF injection, and immunohistochemical analysis revealed that LC3 colocalized in nerve fibers. Electron microscopic analysis revealed that autophagosomes were present in axons and glia, although autophagosome numbers increased significantly after ripasudil injection only in axons. Conclusions: These results suggest that ripasudil-enhanced intra-axonal autophagy is at least partly involved in axonal protection.

Axonal protection by thioredoxin-1 with inhibition of interleukin-1ß in TNF-induced optic nerve degeneration.

Interleukin (IL)-1ß, a proinflammatory cytokine, is a key mediator in several acute and chronic neurological diseases. Thioredoxin-1 (TRX1) acts as an antioxidant and plays a protective role in certain neurons. We examined whether exogenous TRX1 exerts axonal protection and affects IL-1ß levels in tumor necrosis factor (TNF)-induced optic nerve degeneration in rats. Immunoblot analysis showed that IL-1ß was upregulated in the optic nerve after intravitreal injection of TNF. Treatment with recombinant human (rh) TRX1 exerted substantial protective effects against TNF-induced axonal loss. The increase in the IL-1ß level in the optic nerve was abolished by rhTRX1. Treatment with rhTRX1 also significantly inhibited increased glial fibrillary acidic protein (GFAP) levels induced by TNF. Immunohistochemical analysis showed substantial colocalization of IL-1ß and GFAP in the optic nerve after TNF injection. These results suggest that IL-1ß is upregulated in astrocytes in the optic nerve after TNF injection and that exogenous rhTRX1 exerts axonal protection with an inhibitory effect on IL-1ß.

Correlation Between Near-Vision Acuity and the Incidence of Peritoneal Dialysis-Related Infections.

Peritoneal dialysis (PD)-related infections (PDIs) such as peritonitis, exit-site infection, and tunnel infection are serious complications affecting patients on PD. Because patients with diabetes (DM) and of older age have increased in number in Japan, the number of patients with visual impairment is estimated also to have increased. Near vision is necessary for performing proper PD daily care. However, no studies have reported whether visual impairment is likely to increase the risk of PDIs.Our study included 31 PD patients (16 men, 15 women; mean age: 61.5 ± 11.8 years; mean PD duration: 27.3 ± 20.3 months; 38.7% with DM; 54.8% wearing glasses) who performed their own PD care. At our facility and related facilities, we used a standard near-vision test chart, which classifies vision into 12 grades, from 0.1 (poor) to 1.5 (clear), to assess near-vision binocular visual acuity in those patients between March 2015 and September 2015. In addition, we retrospectively examined the medical records of the patients to determine their history of PDIs. We then evaluated the correlation between near-vision acuity and the incidence of PDIs.Mean measured near-vision acuity was 0.61 ± 0.29, and we observed no significant difference in the visual acuity of patients with and without DM (0.55 ± 0.31 vs. 0.63 ± 0.26 respectively, p = 0.477). In addition, we observed no significant difference in the incidence of PDIs between patients with and without DM (1.298 ± 1.609 per year vs. 1.164 ± 0.908 per year respectively, p = 0.804). We did not find a correlation between near-vision acuity and the incidence of PDIs (r = -0.071, p = 0.795).

Axonal protection by short-term hyperglycemia with involvement of autophagy in TNF-induced optic nerve degeneration.

Previous reports showed that short-term hyperglycemia protects optic nerve axons in a rat experimental hypertensive glaucoma model. In this study, we investigated whether short-term hyperglycemia prevents tumor necrosis factor (TNF)-induced optic nerve degeneration in rats and examined the role of autophagy in this axon change process. In phosphate-buffered saline (PBS)-treated rat eyes, no significant difference in axon number between the normoglycemic (NG) and streptozotocin (STZ)-induced hyperglycemic (HG) groups was seen at 2 weeks. Substantial degenerative changes in the axons were noted 2 weeks after intravitreal injection of TNF in the NG group. However, the HG group showed significant protective effects on axons against TNF-induced optic nerve degeneration compared with the NG group. This protective effect was significantly inhibited by 3-methyladenine (3-MA), an autophagy inhibitor. Immunoblot analysis showed that the LC3-II level in the optic nerve was increased in the HG group compared with the NG group. Increased p62 protein levels in the optic nerve after TNF injection was observed in the NG group, and this increase was inhibited in the HG group. Electron microscopy showed that autophagosomes were increased in optic nerve axons in the HG group. Immunohistochemical study showed that LC3 was colocalized with nerve fibers in the retina and optic nerve in both the NG and HG groups. Short-term hyperglycemia protects axons against TNF-induced optic nerve degeneration. This axonal-protective effect may be associated with autophagy machinery.

Zoledronic acid enhances antitumor efficacy of liposomal doxorubicin.

Previously, we found that the injection of zoledronic acid (ZOL) into mice bearing tumor induced changes of the vascular structure in the tumor. In this study, we examined whether ZOL treatment could decrease interstitial fluid pressure (IFP) via change of tumor vasculature, and enhance the antitumor efficacy of liposomal doxorubicin (Doxil®). When ZOL solution was injected at 40 µg/mouse per day for three consecutive days into mice bearing murine Lewis lung carcinoma LLC tumor, depletion of macrophages in tumor tissue and decreased density of tumor vasculature were observed. Furthermore, ZOL treatments induced inflammatory cytokines such as interleukin (IL)-10 and -12, granulocyte-macrophage colony-stimulating factor (GM-CSF) and tumor necrosis factor (TNF)-α in serum of LLC tumor-bearing mice, but not in normal mice, indicating that ZOL treatments might induce an inflammatory response in tumor tissue. Furthermore, ZOL treatments increased antitumor activity by Doxil in mice bearing a subcutaneous LLC tumor, although they did not significantly increase the tumor accumulation of doxorubicin (DXR). These results suggest that ZOL treatments might increase the therapeutic efficacy of Doxil via improvement of DXR distribution in a tumor by changing the tumor vasculature. ZOL treatment can be an alternative approach to increase the antitumor effect of liposomal drugs.

Axonal protection by brimonidine with modulation of p62 expression in TNF-induced optic nerve degeneration.

PURPOSE: The p62, also called sequestosome 1 (SQSTM1), plays a crucial role in tumor necrosis factor (TNF)-induced optic nerve degeneration. Brimonidine has been shown to have protective effects on retinal ganglion cell bodies, although its role in their axons remains to be examined. We determined whether brimonidine modulates axonal loss induced by TNF and affects the expression of p62 in the optic nerve. METHODS: Experiments were performed on adult male Wistar rats that received an intravitreal injection of 10 ng TNF alone or simultaneous injection of TNF and 2, 20, or 200 pmol of brimonidine tartrate. The expression of p62 in the optic nerve was examined by immunoblot analysis. The effects of brimonidine on axons were evaluated by counting axon numbers 2 weeks after intravitreal injection. RESULTS: Intravitreal injection of brimonidine exerted substantial axonal protection against TNF-induced optic nerve degeneration. Immunoblot analysis showed that p62 was upregulated in the optic nerve after intravitreal injection of TNF, and that this increase was completely inhibited by brimonidine. Treatment with brimonidine alone also significantly decreased p62 protein levels in the optic nerve compared with the basal level. CONCLUSIONS: These results suggest that the modulation of p62 levels in the optic nerve by brimonidine may be involved partly in its axonal protection.

Axonal protection by modulation of p62 expression in TNF-induced optic nerve degeneration.

p62, which is also called sequestosome 1 (SQSTM1), plays a critical role in neuronal cell death. However, the role of p62 in axonal degeneration remains unclear. We evaluated whether the modulation of p62 expression may affect axonal loss in tumor necrosis factor (TNF)-induced optic nerve degeneration. Immunoblot analysis showed that p62 was upregulated in the optic nerve after intravitreal injection of TNF. Treatment with p62 small interfering RNA (siRNA) exerted a partial but significant protective effect against TNF-induced axonal loss. Rapamycin exerted substantial axonal protection after TNF injection. We found that the increase in p62 was significantly inhibited by p62 siRNA. Treatment with rapamycin also significantly inhibited increased p62 protein levels induced by TNF. These results suggest that the upregulation of p62 may be involved in TNF-induced axonal degeneration and that decreased p62 levels may lead to axonal protection.

Axonal protection via modulation of the amyloidogenic pathway in tumor necrosis factor-induced optic neuropathy.

PURPOSE: To examine the changes in and localization of phosphorylated presenilin1 (p-PS1) and amyloid precursor protein (APP) in the optic nerve after intravitreal injection of TNF and to investigate the role of γ-secretase in the cleavage of APP in optic nerve degeneration. METHODS: Groups of rats were euthanatized at 1 or 2 weeks after intravitreal injection of TNF. Levels of p-PS1 protein in the optic nerve were determined by immunoblotting and immunohistochemistry. The localization of APP was determined by immunohistochemistry, and its downstream cleavage was determined by immunoprecipitation using 6E10 antibody followed by immunoblotting with an APP intracellular domain (AICD) antibody. The effect of a γ-secretase inhibitor on TNF-induced optic nerve degeneration was determined by counting the number of axons. RESULTS: p-PS1 was increased in the optic nerve after TNF injection and was found to colocalize with vimentin and glial fibrillary acidic protein, markers of astrocytes. Immunoprecipitation using 6E10 antibody followed by immunoblotting with AICD antibody revealed an increase in γ-secretase activation in the optic nerve after TNF injection, which was inhibited by treatment with the γ-secretase inhibitor. Moreover, γ-secretase inhibition significantly prevented the loss of axons in the optic nerve after TNF injection. CONCLUSIONS: The increase in p-PS1 and activation of γ-secretase in the optic nerve may be associated with TNF-induced axonal degeneration. Modulation of γ-secretase activity may be useful for the treatment of TNF-related optic neuropathy.