Retinal imaging in Alzheimer's and neurodegenerative diseases.

In the last 20 years, research focused on developing retinal imaging as a source of potential biomarkers for Alzheimer's disease and other neurodegenerative diseases, has increased significantly. The Alzheimer's Association and the Alzheimer's & Dementia: Diagnosis, Assessment, Disease Monitoring editorial team (companion journal to Alzheimer's & Dementia) convened an interdisciplinary discussion in 2019 to identify a path to expedite the development of retinal biomarkers capable of identifying biological changes associated with AD, and for tracking progression of disease severity over time. As different retinal imaging modalities provide different types of structural and/or functional information, the discussion reflected on these modalities and their respective strengths and weaknesses. Discussion further focused on the importance of defining the context of use to help guide the development of retinal biomarkers. Moving from research to context of use, and ultimately to clinical evaluation, this article outlines ongoing retinal imaging research today in Alzheimer's and other brain diseases, including a discussion of future directions for this area of study.

Indirect Traumatic Optic Neuropathy in Mild Chronic Traumatic Brain Injury.

Purpose: To analyze the clinical presentation and optical coherence tomography (OCT) findings in indirect traumatic optic neuropathy (ITON) in veterans with chronic mild traumatic brain injury (mTBI). Methods: This retrospective study is the first to describe the OCT pattern of subclinical to mild ITON in veterans with chronic mTBI. The thicknesses of the macular ganglion cell layer (mGCL), peripapillary retinal nerve fiber layer (pRNFL), and subfoveal choroidal layer were analyzed in young veterans who had mTBI of >6 months' duration and either blunt head injury or improvised explosive device (IED) concussions. Results: Three major OCT findings were demonstrated: (1) temporal pRNFL thinning was associated with subclinical TON in the eyes of chronic mTBI patients compared with controls; within mTBI subjects, nasal mGCL thinning at the 3-mm modified Early Treatment Diabetic Retinopathy Study circle diameter distance from the fovea correlated with the corresponding temporal retinal nerve fiber layer thinning; (2) inner (1 mm) superior thinning was greater than that of the temporal mGCL in blunt head injury and could potentially distinguish it from IED concussive head trauma; and (3) subfoveal choroidal thinning was significantly worse in eyes of mTBI patients compared with those of controls. Conclusions: These OCT findings may contribute to the understanding of the spectrum of visual injuries resulting from head trauma.

Nonvascular retinal imaging markers of preclinical Alzheimer's disease.

INTRODUCTION: In patients with Alzheimer's disease (AD) and mild cognitive impairment, structural changes in the retina (i.e., reduced thicknesses of the ganglion cell and retinal nerve fiber layers and inclusion bodies that appear to contain beta-amyloid protein [Ab]) have been previously reported. We sought to explore whether anatomic retinal changes are detectable in the preclinical stage of AD. METHODS: A cross-sectional study (as part of an ongoing longitudinal cohort study) involving 63 cognitively normal adults, all of whom have a parent with AD and subjective memory complaints. We compared neocortical amyloid aggregation (florbetapir PET imaging) to retinal spectral domain optical coherence tomography (SD-OCT) markers of possible disease burden. Retinal biomarkers, including the number and surface area of retinal inclusion bodies and the thickness of retinal neuronal layers, were compared across groups with high vs. low neocortical beta-amyloid load. RESULTS: The surface area of inclusion bodies increased as a function of cortical amyloid burden. Additionally, there was a trend toward a selective volume increase in the inner plexiform layer (IPL; a layer rich in cholinergic activity) of the retina in Aß+ relative to Aß- participants, and IPL volume was correlated with the surface area of retinal inclusion bodies. DISCUSSION: These initial results suggest that retinal imaging may be a potential cost-effective and noninvasive technique that can be used to identify those at-risk for AD. Layer-specific changes in the IPL and their association with surface area of inclusion bodies are discussed as a possible reflection of early inflammatory processes associated with cholinergic disruption and concurrent Ab accumulation in the neocortex.

Structural diversity of bimetallic rhodium and iridium half sandwich dithiolato complexes.

The synthesis of a range of rhodium(iii) and iridium(iii) half sandwich complexes with aryl dithiolato ligands of varying geometry and flexibility are reported. These include dinuclear [Cp*M(S-R-S)]2 complexes 3b and 4b, M = Rh, Ir; S-R-S = naphthalene-1,8-dithiolate (b) and four dinuclear complexes bearing bridging dithiolate ligands [(Cp*M)2(µ2-Cl)(µ2-S-R-S)]Cl 3c, 4c, 5b, 6b, M = Rh, Ir; S-R-S = naphthalene-1,8-dithiolate (b) or acenaphthene-5,6-dithiolate (c). The introduction of a less rigid biphenyl dithiolate backbone resulted in the tetranuclear dicationic complex [(Cp*Rh)4(S-R-S)3]Cl2 (3d), S-R-S = biphenyl-2,2'-dithiolate (d) with dithiolate ligands in two different bridging modes. All new complexes were fully characterised by multinuclear NMR, IR, Raman and MS spectroscopy and single crystal X-ray diffraction.

Indocyanine green loaded liposome nanocarriers for photodynamic therapy using human triple negative breast cancer cells.

BACKGROUND: The goal of the current research is to evaluate the potential of photodynamic therapy (PDT) in the treatment of triple negative breast cancer (TNBC) with the development of a theranostic thermosensitive liposome platform to deliver indocyanine green (ICG) as the near-infrared (NIR) photosensitizer excited by an 808 nm diode laser. METHODS: In the PDT protocol, an optimized thermosensitive liposome formulation is investigated to formulate ICG as the photosensitizer, which is exited by laser light at the wavelength of 808 nm delivered by a fiber-coupled laser system. ICG in both free solution and thermosensitive liposomal formulation were evaluated as the NIR photosensitizer and compared in the PDT treatment on a panel of triple negative breast cancer cell lines along with the nontumorigenic mammary epithelial cell line MCF-10A. In addition to cytotoxicity, and clonogenic survival assessment, the role of DNA double strand break damage was evaluated. RESULTS: Both MTT and clonogenic assays revealed that PDT using ICG inhibited the growth of several TNBC cell lines as well as the non-tumorigenic human breast epithelial cell line MCF-10A; and the liposomal formulation of ICG did not compromise the in vitro treatment potency, though free ICG performed slightly more effective in certain cell lines, but was not statistically significant. Cell viability was dose dependent in regards to ICG concentration and irradiation energy. Interestingly, PDT using the described protocol was more potent to inhibit the growth of MDA-MB-468 and HCC-1806 cells, coinciding with the observation that these cells are more sensitive toward DNA damaging agents. In comparison, cell lines HCC-70, BT-549, and MCF-10A were found to have less of an inhibitory effect. Furthermore, substantial DNA double strand breaks (DSBs) were observed 30 min after the PDT treatment via a γ-H2AX staining assay. PDT induced DNA damage has the potential to lead to mutagenicity, which may have various responses depending on the repair capabilities of the cells. CONCLUSION: Our results suggest that PDT using indocyanine green loaded liposomes were effective in inhibiting tumor cell growth to varying extents with higher responses observed for MDA-MB-468 and HCC-1806 cells.