GENE THEAPY FOR ETINAL DISEASES

Retinal diseases are a major cause of irreversible blindness. These conditions can be caused genetically or acquired later in life. Complex diseases have both genetic and acquired counterparts. Most common forms of multifactorial retinal diseases include macular degeneration, glaucoma, diabetic retinopathy, and retinoblastoma. Inherited retinal degenerations, on the other hand, are entirely linked to mutations in retinal neurons and their underlying epithelium. Retinal cell death is the main cause of vision loss in many blinding conditions, for which gene and cell therapy approaches offer intervention at various stages.

Gene therapy is an emerging therapeutic approach to treat, cure, or prevent a disease by providing a gene with therapeutic action. Diseases associated with loss-of-function mutations can be treated by gene replacement therapy (also referred to as gene supplementation), whereas those associated with gain-of-function mutations require eradication of mutant alleles in addition to supplementing the gene. In all instances, the genetically modifying factors (DNA or RNA and/or their interacting proteins) need to be delivered into the relevant target cells. Most gene therapy studies use viral vectors, such as adenovirus (Ad), adeno-associated virus (AAV), or lentivirus (LV), to enable gene delivery to the retina. Two local administration routes allow viral vectors to access retinal cells. Viral vectors can either be injected into the vitreous cavity via an intravitreal injection, or they can be injected into the subretinal space, created through a transient retinal detachment. Intravitreal injections deliver the vector in proximity to the retinal ganglion cells and are the preferred delivery route for targeting the inner retina. Subretinal injections deliver vectors between the photoreceptors and their underlying retinal pigment epithelium (RPE). As most inherited retinal degenerations are caused by mutations found in the photoreceptor and RPE cells, subretinal injections have been used in most gene therapy studies.

Depending on the cell target, Ad, LV, and AAV have been studied. After subretinal delivery both Ad and LV transduce the RPE efficiently. Ad, however, has been associated with cytotoxic T lymphocyte-mediated removal of the transduced cells that express the encoded Ad proteins,⁴ leading to transient gene expression. More recently, helper-dependent Ad vectors devoid of sequences encoding viral proteins have been developed and shown to target the RPE stably.^5,6 Thus far, photoreceptor transduction remains elusive with Ad and LV vectors despite the great diversity of new serotypes and pseudotype.

. Approved therapies like Luxturna target the RPE65 gene mutation for conditions like Leber Congenital Amaurosis, while other gene therapies are in trials for retinitis pigmentosa by replacing genes like RPGR. Delivery methods include subretinal injection to target photoreceptors and RPE cells or intravitreal injection for inner retinal cells.  

How it Works

1. 1. Gene Replacement:

The primary approach is to introduce a correct, healthy copy of a gene that is mutated in the patient's retinal cells. 

2. 2. Delivery Vector:

Harmless viral vectors, most commonly adeno-associated viruses (AAV), are used to carry the genetic material into the target cells. 

3. 3. Cellular Repair:

The new genetic material enables the cells to produce the necessary proteins to function correctly and survive longer, slowing or halting vision loss. 

Approved and Investigational Therapies

• Luxturna (Voretigene neparvovec-rzyl):

The first FDA-approved gene therapy for inherited blindness, treating conditions caused by mutations in the RPE65 gene, such as Leber congenital amaurosis. 

• Retinitis Pigmentosa (RP) Therapies:

Several therapies are in development for different forms of RP, like the one targeting the RPGR gene. 

Delivery Methods

• Subretinal Injection:

Involves detaching the retina temporarily to inject the viral vector directly into the space between the photoreceptors and the retinal pigment epithelium (RPE), the main target for many inherited retinal diseases. 

• Intravitreal Injection:

A safer and simpler method where the vector is injected into the vitreous humor (the gel-like substance filling the eye), allowing access to a wider area of the retina, particularly for targeting inner retinal cells. 

Challenges and the Future

• Specific Targets:

Gene therapy is most effective for recessive genetic disorders but requires different approaches, such as gene editing or suppression, for other types of mutations. 

HOW DO CHAMELEONS CHANGE COLOR ?

 HOW DO CHAMELONS CHANGE COLORS ?

Why do chameleons change colors?

Chameleons have built a pretty solid reputation upon a commonly held belief: They can stealthily blend into their surroundings. But it turns out one of those supposed facts isn't quite right — in fact, everything you think you know about chameleons and their color-changing capabilities is likely backward.

Chameleons don't actually change colors to match their enviornment. when chameleons are relaxed, they are mostly green; which allows them to naturally blend into their habitat in the forest canopy. These lizards don't change their appearance to fit in, but rather to stand out. 

They change colors when they feel threatened, or annoyed or just wanna make statement. they transform into Living Mood Rings. the faster their skin changes color, the more excited they are.

How do they do it ?

For long, scientists thought that chameleons change colors by spreading out pigments in their cells, like squids or octopuses.  but biologists and physicists somewhat recently realized that something way complex is going on. 

Just below the surface of their skin is a layer of cells called iridophores, tiny nano-scale salt crystals made from guanine. Tese crystals are arranged into a three dimensional lattice. when light hits the lattice, it shatters into different wavelengths, some are absorbed and some are bounced back. A chameleon can adjust the wavelengths of light reflected in these tiny crystals by either tightening or relaxing their skin, which changes the spacing of the cells. when the distance changes, the crystals reflect a different wavelength of light. the result is a dramatic shift in color. f the distance between the layers is small, it reflects small wavelengths, like blue; if the distance is large it reflects larger wavelengths- for example, red.

When the animal is relaxed, the cells stay close together and reflect short wavelengths, like blue. A rush of excitement pushes those cells farther apart, enabling each iridophore to reflect longer wavelengths, like red, orange and yellow.

Why are they normally green ?

When the animal is relaxed, the cells stay close together and reflect short wavelengths, like blue. A rush of excitement pushes those cells farther apart, enabling each iridophore to reflect longer wavelengths, like red, orange and yellow.

Additionally, chameleons have pigment cells called chromatophores. Among these chromatophores are xanthophores, which contain yellow pigments. When the blue light from the iridophore cells passes through the yellow pigments in the xanthophores, the resulting color is green. This is similar to how mixing blue and yellow paint results in green.

However, not all chameleons can go Technicolor—some can only range from green, brown and gray. But panther chameleons, found in Madagascar and the focus of this study, can exhibit exotic blues, yellows, greens and reds. And now we can thank crystals for the show.  

#BlackGirlMagic : Mae Jemison

"Don't let anyone rob you of your imagination, your creativity, or your curiosity. It's your place in the world; it's your life. Go on and do all you can with it, and make it the life you want to live."

As a doctor, engineer, and a NASA astronaut, Dr. Mae carol Jemison has always reached for the stars. I992, she became the first woman of color to travel in space. 

Mae Jemison was born on 17 October in Decatur, Alabama. After a few years, her family moved to Chicago, Illinois. 

in addition to her love for dance, Jemison knew that she wanted to study science and go to space from a young age. Mae grew up watching Apollo airings, but was frustrated that there were no female astronauts. However, she was inspired by the African American actress Nichelle Nichols who played lieutenant Uhura in the star trek television show. Although both her parents were supportive, teachers discouraged Jemison.

In 1973, at age 16, she left Chicago to attend Stanford university in California.

As one of the only African American students in her class, Jemison experienced racial discrimination in school. She served as president of the black student union. in 1977 she received undergraduate degrees in chemical engineering and African-American studies. While at Stanford she also pursued studies related to space and first considered applying to NASA. After graduating from Stanford university, she attended the Cornell medical school. There, she travelled to Cuba to lead a study and worked at a Cambodian refugee camp In Thailand. After graduating with a doctorate in medicine in 1981, she interned at the Los Angeles County medical centre in 1982 and practiced general medicine. 

Jemison joined the peace corps in 1983 and worked as a medical officer for two years in Africa. She supervised the peace corps pharmacy, laboratory, medical staff and implementing guidelines for health and safety issues. 

However, once sally ride became the first American woman in space, she applied to the astronaut program in 1985 but after the Space Shuttle challenger exploded in 1986 NASA took a break from selecting new people. She reapplied again in 1987 and was one of the 15 people chosen out of over 2,000 selected for NASA Astronaut Group 12, the first group chosen after the Challenger explosion. After being selected, Jemison trained with NASA and worked on projects at the Kennedy Space Center in Florida and the Shuttle Avionics Integration Laboratory. 

She received her first mission on September 12, 1992. Jemison as the science mission specialist and six other astronauts went into space on the space shuttle Endeavor for STS-47. in 1992 it spent eight days in space. During the mission, 44 life science and materials processing experiments were carried out by the crew while orbiting Earth 126 times. It returned on September 20, 1992 This voyage made Jemison the first African-American woman in space.

Dr. Jemison started The Jemison Group, Inc which investigates the social and cultural impacts of technological advancements.  She is founder of the non-profit Dorothy Jemison Foundation for Excellence. She started The Earth We Share™, an international science literacy curriculum and program that builds student critical thinking and problem-solving skills as they gain science knowledge and skills, and trains school teachers in experiential education. 

Dr. Jemison is an inductee of the National Women’s Hall of Fame, the National Medical Association Hall of Fame, and Texas Science Hall of Fame and recipient of the National Organization for Women’s Intrepid Award and the Kilby Science Award among many honours

She is the principal for the 100 Year Starship Project provides guidance and direction for the foundation in fulfilling its goal of ensuring all capabilities for a successful human journey to another star will exist by 2112.

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