SASP Modulator Compositions for Ocular Senescence Control
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Solution Overview
Problem
Cellular senescence contributes to various detrimental diseases and conditions, including vascular ocular diseases, while its beneficial aspects in tissue repair and wound healing are underexplored, necessitating targeted modulation of the senescence-associated secretory phenotype (SASP) for therapeutic intervention.
Innovation Solution
Compositions comprising SASP modulators and senescence attenuators, such as IRE1α and SEMA3A inhibitors, are administered to modulate cellular senescence, reducing SASP activity and promoting vascular repair in ocular tissues, thereby treating or preventing vascular eye diseases like diabetic retinopathy and age-related macular degeneration.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If cellular senescence is allowed to proceed naturally, then tissue repair and wound healing are enhanced, but detrimental diseases and conditions including vascular ocular diseases are aggravated
Solution Approach 1:
The patent applies local quality by differentiating the treatment approach based on the desired outcome: promoting senescence in contexts requiring tissue repair while inhibiting senescence in contexts where it drives pathology. The composition enables selective modulation of SASP factors to achieve beneficial local effects without systemic side effects.
Solution Approach 2:
The patent changes the parameter of SASP activity through the use of modulators that can either enhance or suppress specific secreted factors. By adjusting the level and type of SASP factors present, the treatment can shift between promoting tissue repair and preventing disease progression depending on the clinical context.
2Productivity
If SASP activity is enhanced to promote tissue repair, then wound healing is improved, but harmful secreted factors may contribute to disease progression
Solution Approach 1:
The patent segments the SASP into individual factor components and selectively modulates specific factors rather than treating the secretory phenotype as a unified entity. This allows enhancement of beneficial factors while suppressing harmful ones, achieving wound healing promotion without disease progression.
Solution Approach 2:
The patent uses intermediary molecules that specifically bind to and modulate individual SASP factors. These intermediaries act as mediators between the senescent cell and the extracellular environment, selectively enhancing or suppressing the activity of specific secreted factors to achieve desired therapeutic outcomes.
Data Source
Figure 1A~1B
Figure 1C
Figure 1D~1E
AI summary
Described herein are compositions and methods for modulating cellular senescence of a cell or induction of the senescence-associated secretory phenotype (SASP) in a cell. The methods generally comprise modulating the level or activity of IRE1a as a mean to control cellular senescence and induction of the SASP. Also described are methods for treating and preventing ocular vascular diseases comprising contacting cells in an eye of a subject with a biguanide compound and ophthalmic compositions comprising a biguanide compound.