Abstract: It is disclosed herein that RPE degeneration in human cell culture and in mouse models is driven by a non-canonical inflammasome pathway that results in activation of caspase-4 (also known as caspase-11 in mouse) and caspase-1, and requires cyclic GMP-AMP synthase (cGAS)-dependent interferon-? (IFN-?) production and gasdermin D-dependent interleukin-18 (IL-18) secretion. Reduction of DICER1 or accumulation of Alu RNA triggers cytosolic escape of mitochondrial DNA, which engages cGAS. Collectively, these data highlight an unexpected role for cGAS in responding to mobile element transcripts, reveal cGAS-driven interferon signaling as a conduit for mitochondrial damage-induced NLRP3 activation, and expand the immune sensing repertoire of cGAS and caspase-4 to non-infectious human disease. Coupled with the unexpected result that caspase-4, gasdermin D, IFN-?, and cGAS are elevated in the RPE of human eyes with geographic atrophy, these findings also identify new targets for a major cause of blindness.

Abstract: Therapeutic uses P2X7 inhibition and inhibition of IRAK1 and/or IRAK4, methods protecting a cell, and screening methods for identifying inhibitors are described herein.

Abstract: Provided are methods for treating macular degeneration, optionally macular degeneration, in subject in need thereof. In some embodiments, the methods include administering to a subject in need thereof a therapeutically effective amount of fluoxetine in an amount and via a route sufficient to treat or prevent development of macular degeneration in the subjects. Also provided are methods for inhibiting activation of an NLRP3-ASC inflammasome in the subjects, inhibiting ASC speck formation in the subjects, inhibiting Alu RNA-induced RPE degeneration in the subjects, and treatment and/or prevention of the development of diseases, disorders, and/ or conditions.

Abstract: Therapeutic uses P2X7 inhibition and inhibition of IRAK1 and/or IRAK4, methods protecting a cell, and screening methods for identifying inhibitors are described herein.

Abstract: The present disclosure relates to compounds and compositions that inhibit the NLRP3 inflammasome, for example, or a pharmaceutically acceptable salt thereof. Also disclosed are methods for treating, and in particular methods for treating macular degeneration, e.g., dry age-related macular degeneration (AMD) and wet AMD, Alzheimer's disease, multiple sclerosis, and Parkinson's disease, using compounds and compositions that inhibit the NLRP3 inflammasome.

Abstract: The present disclosure relates to compositions and methods for treating retinal damage and/or retinal degradation. More specifically, this disclosure relates to methods for treating degradation of the retinal pigment epithelium by administering compositions comprising a nucleoside and/or a nucleoside or nucleotide reverse transcriptase inhibitor.

Abstract: Methods for treating and/or inhibiting progression of diseases, conditions, and/or disorders. In some embodiments, the methods include administering to as subject in need thereof a composition that includes a nucleoside reverse transcriptase inhibitor (NRTIs), an NRTI metabolite, an NRTI analog, a pharmaceutically acceptable salt and/or metabolite thereof, a prodrug of an NRTI, or any combination thereof. Also provided are methods for inhibiting development of macular degeneration in subjects; methods for inhibiting development and/or progression of viral infection and/or a disease, condition, disorder, and/or symptom associated therewith in a subject in need thereof; methods for inhibiting development and/or progression of acute respiratory distress syndrome in subjects; methods for inhibiting development and/or progression of cytokine storm syndrome in subjects; methods for inhibiting development and/or progression of fibrosis in subjects, and compositions for use in the presently disclosed methods.

Abstract: The present disclosure relates to compositions and methods for treating retinal damage and/or retinal degradation. More specifically, this disclosure relates to methods for treating degradation of the retinal pigment epithelium by administering compositions comprising a nucleoside and/or a nucleoside or nucleotide reverse transcriptase inhibitor.

Abstract: Provided are nucleotide sequences encoding polypeptides with ribonuclease III activity, wherein the nucleotide sequences have been modified to reduce their regulation by miRNAs. In some embodiments, the nucleotide sequences are at least 50% and as much as 100% identical to SEQ ID NO: 20 or SEQ ID NO: 22, and/or encode polypeptides that are at least 90% percent identical to SEQ ID NO: 23. Also provided are vectors and host cells that include the nucleotide sequences, methods for expressing the nucleotide sequences in cells, tissues, and organs, which in some embodiments can be in the eye of a subject in need thereof, methods for preventing and/or treating development of diseases or disorders and/or for restoring undesirably low DICER1 expression using the nucleotide sequences, and pharmaceutical compositions that have the presently disclosed nucleotide sequences.

Abstract: Provided are methods for treating and/or preventing diseases, disorders, and/or conditions associated with NLR family CARD domain containing 4 (NLRC4) inflammasome biological activities. In some embodiments, the method include administering to a subject in need thereof a composition that includes a nucleoside reverse transcriptase inhibitor (NRTI). Also provided are methods for inhibiting NLRC4-induced caspase-1 activation in cells, methods for inhibiting NLRC4-induced IL-I? release from cells, methods for inhibiting Alu-induced retinal pigmented cell (RPE) degeneration in subjects, and compositions for use in the presently disclosed methods.

Abstract: Provided are methods and compositions for the treatment or prevention of ocular angiogenesis and neovascularization. Administration of inhibitors of the CCR3 receptor or its ligands eotaxin (CCL11), eotaxin-2 (CCL24) or eotaxin-3 (CCL26) inhibits ocular angiogenesis.

Abstract: Methods for treating and/or inhibiting progression of neurological diseases, conditions, and/or disorders. In some embodiments, the methods include administering to as subject in need thereof a composition that includes a reverse transcriptase inhibitor. Also provided are methods for inhibiting development of amyloid beta peptide (A?) in subjects, methods for inhibiting microglial cell death, and composition for use in the presently disclosed methods.

Abstract: The present disclosure relates to modified nucleoside reverse transcriptase inhibitors (NRTIs), such as and compositions thereof, as well as methods useful for treating retinal damage and/or retinal degradation/retinal degeneration, for inhibiting inflammasome activation by Alu RNA associated with a cell, for reducing ATP-induced permeability of a cell, for reducing an amount of mitochondrial reactive oxygen species in a cell, and for reducing an amount of mitochondrial reactive oxygen species in a cell.

Abstract: Therapeutic uses P2X7 inhibition and inhibition of IRAK1 and/or IRAK4, methods protecting a cell, and screening methods for identifying inhibitors are described herein.

Abstract: Provided are method for treating age-related macular degeneration (AGE), and/or preventing the occurrence or progression thereof in a subject in need thereof. In some embodiments, the methods include administering to the subject in need thereof a composition that has an effective amount of an inhibitor of reverse transcriptase (RTase) activity. Also provided are methods for protecting retinal pigmented epithelium (RPE) cells, retinal photoreceptor cells, and/or choroidal cells; methods for treating geographic atrophy of the eye, and/or for preventing occurrence or progression thereof; and pharmaceutical compositions for treating AGE and/or GA and/or for preventing the occurrence or progression thereof; and/or for protecting RPE cells, retinal photoreceptor cells, and/or choroidal cells.

Abstract: The present disclosure relates to compounds, compositions, and methods useful for treating retinal damage and/or retinal degradation/retinal degeneration, for inhibiting inflammasome activation by Alu RNA associated with a cell, for reducing ATP-induced permeability of a cell, for reducing an amount of mitochondrial reactive oxygen species in a cell, and for reducing an amount of mitochondrial reactive oxygen species in a cell. The present disclosure further relates to compounds, compositions, and methods for use in protecting an RPE cell and/or for treating, including prophylactic and therapeutic treatment, of conditions associated with retinal damage and/or degradation including, but not limited to, dry age related macular degeneration (AMD) and wet AMD, Alzheimer disease, various forms of arthritis, atherosclerosis, diabetes mellitus, chronic obstructive pulmonary disease, inflammatory bowel disease, and Duchenne muscular dystrophy.

Abstract: The present disclosure relates to compounds, compositions, and methods useful for treating retinal damage and/or retinal degradation/retinal degeneration, for inhibiting inflammasome activation by Alu RNA associated with a cell, for reducing ATP-induced permeability of a cell, for reducing an amount of mitochondrial reactive oxygen species in a cell, and for reducing an amount of mitochondrial reactive oxygen species in a cell. The present disclosure further relates to compounds, compositions, and methods for use in protecting an RPE cell and/or for treating, including prophylactic and therapeutic treatment, of conditions associated with retinal damage and/or degradation including, but not limited to, dry age related macular degeneration (AMD) and wet AMD, Alzheimer disease, various forms of arthritis, atherosclerosis, diabetes mellitus, chronic obstructive pulmonary disease, inflammatory bowel disease, and Duchenne muscular dystrophy.

Abstract: The present disclosure relates to compounds, compositions, and methods useful for treating retinal damage and/or retinal degradation/retinal degeneration, for inhibiting inflammasome activation by Alu RNA associated with a cell, for reducing ATP-induced permeability of a cell, for reducing an amount of mitochondrial reactive oxygen species in a cell, and for reducing an amount of mitochondrial reactive oxygen species in a cell. The present disclosure further relates to compounds, compositions, and methods for use in protecting an RPE cell and/or for treating, including prophylactic and therapeutic treatment, of conditions associated with retinal damage and/or degradation including, but not limited to, dry age related macular degeneration (AMD) and wet AMD, Alzheimer disease, various forms of arthritis, atherosclerosis, diabetes mellitus, chronic obstructive pulmonary disease, inflammatory bowel disease, and Duchenne muscular dystrophy.

Abstract: The present disclosure relates to compositions and methods for treating retinal damage and/or retinal degradation. More specifically, this disclosure relates to methods for treating degradation of the retinal pigment epithelium by administering compositions comprising a nucleoside and/or a nucleoside or nucleotide reverse transcriptase inhibitor.

Abstract: The present disclosure relates to compositions and methods for treating retinal damage and/or retinal degradation. More specifically, this disclosure relates to methods for treating degradation of the retinal pigment epithelium by administering compositions comprising a nucleoside and/or a nucleoside or nucleotide reverse transcriptase inhibitor.