Faisal Ahmed

Studies on the singlet oxygen scavenging mechanism of human macular pigment

It is thought that direct quenching of singlet oxygen and scavenging free radicals by macular pigment carotenoids is a major mechanism for their beneficial effects against light-induced oxidative stress. Corresponding data from human tissue remains unavailable, however. In the studies reported here, electron paramagnetic resonance (EPR) spectroscopy was used to measure light-induced singlet oxygen generation in post-mortem human macula and retinal pigment epithelium/choroid (RPE/choroid). Under white-light illumination, production of singlet oxygen was detected in RPE/choroid but not in macular tissue, and we show that exogenously added macular carotenoids can quench RPE/choroid singlet oxygen. When the singlet oxygen quenching ability of the macular carotenoids was investigated in solution, it was shown that a mixture of meso-zeaxanthin, zeaxanthin, and lutein in a ratio of 1:1:1 can quench more singlet oxygen than the individual carotenoids at the same total concentration.

Fermi Level Pinning at Electrical Metal Contacts of Monolayer Molybdenum Dichalcogenides

Electrical metal contacts to two-dimensional (2D) semiconducting transition metal dichalcogenides (TMDCs) are found to be the key bottleneck to the realization of high device performance due to strong Fermi level pinning and high contact resistances (Rc). Until now, Fermi level pinning of monolayer TMDCs has been reported only theoretically, although that of bulk TMDCs has been reported experimentally. Here, we report the experimental study on Fermi level pinning of monolayer MoS2 and MoTe2 by interpreting the thermionic emission results. We also quantitatively compared our results with the theoretical simulation results of the monolayer structure as well as the experimental results of the bulk structure. We measured the pinning factor S to be 0.11 and -0.07 for monolayer MoS2 and MoTe2, respectively, suggesting a much stronger Fermi level pinning effect, a Schottky barrier height (SBH) lower than that by theoretical prediction, and interestingly similar pinning energy levels between monolayer and bulk MoS2. Our results further imply that metal work functions have very little influence on contact properties of 2D-material-based devices. Moreover, we found that Rc is exponentially proportional to SBH, and these processing parameters can be controlled sensitively upon chemical doping into the 2D materials. These findings provide a practical guideline for depinning Fermi level at the 2D interfaces so that polarity control of TMDC-based semiconductors can be achieved efficiently.

Photoreceptor avascular privilege is shielded by soluble VEGF receptor-1

Optimal phototransduction requires separation of the avascular photoreceptor layer from the adjacent vascularized inner retina and choroid. Breakdown of peri-photoreceptor vascular demarcation leads to retinal angiomatous proliferation or choroidal neovascularization, two variants of vascular invasion of the photoreceptor layer in age-related macular degeneration (AMD), the leading cause of irreversible blindness in industrialized nations. Here we show that sFLT-1, an endogenous inhibitor of vascular endothelial growth factor A (VEGF-A), is synthesized by photoreceptors and retinal pigment epithelium (RPE), and is decreased in human AMD. Suppression of sFLT-1 by antibodies, adeno-associated virus-mediated RNA interference, or Cre/lox-mediated gene ablation either in the photoreceptor layer or RPE frees VEGF-A and abolishes photoreceptor avascularity. These findings help explain the vascular zoning of the retina, which is critical for vision, and advance two transgenic murine models of AMD with spontaneous vascular invasion early in life. DOI: http://dx.doi.org/10.7554/eLife.00324.001

Targeted intraceptor nanoparticle therapy reduces angiogenesis and fibrosis in primate and murine macular degeneration

Monthly intraocular injections are widely used to deliver protein-based drugs that cannot cross the blood-retina barrier for the treatment of leading blinding diseases such as age-related macular degeneration (AMD). This invasive treatment carries significant risks, including bleeding, pain, infection, and retinal detachment. Further, current therapies are associated with a rate of retinal fibrosis and geographic atrophy significantly higher than that which occurs in the described natural history of AMD. A novel therapeutic strategy which improves outcomes in a less invasive manner, reduces risk, and provides long-term inhibition of angiogenesis and fibrosis is a felt medical need. Here we show that a single intravenous injection of targeted, biodegradable nanoparticles delivering a recombinant Flt23k intraceptor plasmid homes to neovascular lesions in the retina and regresses CNV in primate and murine AMD models. Moreover, this treatment suppressed subretinal fibrosis, which is currently not addressed by clinical therapies. Murine vision, as tested by OptoMotry, significantly improved with nearly 40% restoration of visual loss induced by CNV. We found no evidence of ocular or systemic toxicity from nanoparticle treatment. These findings offer a nanoparticle-based platform for targeted, vitreous-sparing, extended-release, nonviral gene therapy.

Modulation of Quantum Tunneling via a Vertical Two-Dimensional Black Phosphorus and Molybdenum Disulfide p–n Junction

Diverse diode characteristics were observed in two-dimensional (2D) black phosphorus (BP) and molybdenum disulfide (MoS2) heterojunctions. The characteristics of a backward rectifying diode, a Zener diode, and a forward rectifying diode were obtained from the heterojunction through thickness modulation of the BP flake or back gate modulation. Moreover, a tunnel diode with a precursor to negative differential resistance can be realized by applying dual gating with a solid polymer electrolyte layer as a top gate dielectric material. Interestingly, a steep subthreshold swing of 55 mV/dec was achieved in a top-gated 2D BP-MoS2 junction. Our simple device architecture and chemical doping-free processing guaranteed the device quality. This work helps us understand the fundamentals of tunneling in 2D semiconductor heterostructures and shows great potential in future applications in integrated low-power circuits.

Temporal Macular Thinning Associated With X-Linked Alport Syndrome

IMPORTANCE Optical coherence tomography (OCT) findings of temporal macular thinning are important in the diagnosis and prognosis of X-linked Alport syndrome (XLAS). OBJECTIVES To report OCT findings and severity of temporal macular thinning in a cohort with XLAS and to correlate these and other ocular findings with mutation genotype. DESIGN Patients with XLAS underwent genotyping for COL4A5 mutations and complete eye examinations with retinal imaging using spectral domain OCT and fundus photography. Temporal macular thinning was calculated from OCT measurements by comparing the ratio of the retinal thickness of the temporal to the nasal subfields with a published normative database. SETTING University departments of ophthalmology and nephrology. PARTICIPANTS Thirty-two patients from 24 families. MAIN OUTCOME AND MEASURES Temporal thinning index calculated from spectral domain OCT scans. RESULTS All study patients had a mutation associated with the X-linked COL4A5 gene. Eleven different mutations were identified. Eleven of 32 patients (34%) expressed the L1649R mutation. Of a total of 63 eyes with available OCT scans, 44 (70%) had severe pathological temporal macular thinning. The L1649R mutation was associated with the least amount of severe temporal macular thinning and later onset of renal failure. CONCLUSIONS AND RELEVANCE Temporal macular thinning is a prominent sign associated with XLAS, suggesting that OCT measurements are essential in the diagnosis and prognosis of the disease. The L1649R mutation in the COL4A5 gene causes a relatively mild form of XLAS characterized by late-onset renal failure and less frequent, severe temporal macular thinning relative to other COL4A5 mutations. The pathological basis for the retinal abnormalities of XLAS remains to be established.

Spectacle Independence after Cataract Extraction in Post-Radial Keratotomy Patients Using Hybrid Monovision with ReSTOR® Multifocal and TECNIS® Monofocal Intraocular Lenses

Background: We report 2 patients who have undergone radial keratotomy (RK) preceding ReSTOR® multifocal intraocular lens (IOL; Alcon, Fort Worth, Tex., USA) implantation in their nondominant eyes and TECNIS® monofocal IOL (Abbott Medical Optics, Abbott Park, Ill., USA) in their dominant eyes. Methods: Retrospective review of 2 patients who underwent hybrid monovision with ReSTOR® multifocal and TECHNIS® monofocal IOLs at the time of cataract surgery after a remote history of RK. Results: Implantation of the ReSTOR® multifocal and the TECHNIS® monofocal IOLs was successful, with no reported adverse events. The patients were able to achieve spectacle freedom. Conclusion: We report a novel technique for the management of post-RK patients to optimize their chances for spectacle independence.

Recent advances in the diagnosis and management of glaucoma

Reducing intraocular pressure remains the only treatment option in glaucoma, however, prompt evaluation and management can prevent blindness and a lifetime of disability. Our Drug Review outlines the key points and recent advances in diagnosis and management.Reducing intraocular pressure remains the only treatment option in glaucoma, however, prompt evaluation and management can prevent blindness and a lifetime of disability. Our Drug Review outlines the key points and recent advances in diagnosis and management.

Analysis of nodal coverage utilizing image guided radiation therapy for primary gynecologic tumor volumes

PURPOSE To evaluate radiation dose delivered to pelvic lymph nodes, if daily Image Guided Radiation Therapy (IGRT) was implemented with treatment shifts based on the primary site (primary clinical target volume [CTV]). Our secondary goal was to compare dosimetric coverage with patient outcomes. MATERIALS AND METHODS A total of 10 female patients with gynecologic malignancies were evaluated retrospectively after completion of definitive intensity-modulated radiation therapy (IMRT) to their pelvic lymph nodes and primary tumor site. IGRT consisted of daily kilovoltage computed tomography (CT)-on-rails imaging fused with initial planning scans for position verification. The initial plan was created using Varian׳s Eclipse treatment planning software. Patients were treated with a median radiation dose of 45Gy (range: 37.5 to 50Gy) to the primary volume and 45Gy (range: 45 to 64.8Gy) to nodal structures. One IGRT scan per week was randomly selected from each patient׳s treatment course and re-planned on the Eclipse treatment planning station. CTVs were recreated by fusion on the IGRT image series, and the patient׳s treatment plan was applied to the new image set to calculate delivered dose. We evaluated the minimum, maximum, and 95% dose coverage for primary and nodal structures. Reconstructed primary tumor volumes were recreated within 4.7% of initial planning volume (0.9% to 8.6%), and reconstructed nodal volumes were recreated to within 2.9% of initial planning volume (0.01% to 5.5%). RESULTS Dosimetric parameters averaged less than 10% (range: 1% to 9%) of the original planned dose (45Gy) for primary and nodal volumes on all patients (n = 10). For all patients, ≥99.3% of the primary tumor volume received ≥ 95% the prescribed dose (V95%) and the average minimum dose was 96.1% of the prescribed dose. In evaluating nodal CTV coverage, ≥ 99.8% of the volume received ≥ 95% the prescribed dose and the average minimum dose was 93%. In evaluating individual IGRT sessions, we found that 6 patients had an estimated minimal nodal CTV dose less than 90% (range: 78 to 99%) of that planned. With a median follow-up of 42.5 months, 2 patients experienced systemic disease progression at an average of 19.6 months. One patient was found to have a local or regional failure with an average follow-up of 42 months. CONCLUSION Using only 3 dimensional IGRT corrections in gynecological radiation allows excellent coverage of the primary target volume and good average nodal CTV coverage. If IGRT corrections are based on alignment to the primary tumor volume, and is only able to be corrected in 3 degrees, this can create situations in which nodal volumes may be under dosed. Utilizing multiple IGRT sessions appears to average out dose discrepancies over the course of treatment. The implication of underdosing in a single IGRT session needs further evaluation in future studies. Based on the concern of minimum dose to a nodal target volume, these findings may signal caution when using IGRT and IMRT in gynecological radiation patients. Possible techniques to overcome this situation may include averaging shifts between tumor and nodal volume, use of a treatment couch with 6° of freedom, deformable registration, or adaptive planning.

Severe Corticosteroid-Induced Ocular Hypertension Requiring Bilateral Trabeculectomies in a Patient with Takayasu’s Arteritis

We present a rare case of severe corticosteroid-induced ocular hypertension (OHT) after prolonged systemic corticosteroid use in a young woman with Takayasus arteritis. As she did not sufficiently respond to ocular antihypertensive therapies, bilateral enhanced trabeculectomies were required to normalize her intraocular pressures. The systemic side effects of corticosteroids are well known, yet steroid-induced OHT and glaucoma remain silent causes of ocular morbidity. This case highlights the importance of IOP-monitoring in visually asymptomatic patients on systemic corticosteroids. It further emphasizes the need to raise awareness of the potential ocular side effects of steroids amongst physicians, in particular those looking after patients with autoimmune and inflammatory diseases.