MITOCHONDRIA AND EYE DISEASES, Slides of Zoology

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MITOCHONDRIA AND

EYE DISEASES

Presented by- SONALI BAZALA 19MSLSAS DEPARTMENT OF ANIMAL SCIENCES

INTRODUCTION:

 (^) The word mitochondrion comes from two Greek words, mitos means “thread” and chondrion means “granule” or “grain-like”.  (^) Mitochondria are membrane-bound cell organelles that generate most of the chemical energy needed to power the cell's biochemical reactions. Chemical energy produced by the mitochondria is stored in a small molecule called adenosine triphosphate (ATP). Because of the formation of ATP, mitochondria are called the power house of the cell.

STRUCTURE:

 (^) Mitochondria are surrounded by two membranes- Outer membrane and Inner membrane. The outer membrane is smooth and continuous whereas inner membrane forms a no. of infolding called the cristae.  (^) Outer membrane is chemically 40% lipid and 60% proteins and the inner membrane has 80% proteins and 20% lipids and is rich in cardiolipins.  (^) Due to the presence of 2 membranes, the organelle is partitioned into 2 distinct chambers filled with aqueous fluid. a) Outer compartment or intermembrane space b) Inner compartment or matrix.  (^) The enzymes and electron carriers for ATP formation are present only in the inner membrane.  (^) The matrix contains:  (^) Single circular dsDNA  (^) Few RNA molecule  (^) 70s ribosomes  (^) Enzymes for TCA cycle.

FUNCTIONS:

 (^) Mitochondria are the main sites of aerobic respiration.  (^) They are miniature biochemical factories where respiratory substrates are completely oxidised to carbon dioxide and water and energy is stored in the form of ATP.  (^) The energy produced in the mitochondria helps to perform various energy-requiring processes of the cell like muscle contraction, nerve impulse conduction etc.  (^) These bring about the oxidation of carbohydrates, proteins and ß- oxidation of fats.

MITOCHONDRIAL DISEASES

 (^) It is caused due to the mutation at base pair 11778 in mtDNA that affects one of the subunits of complex 1 of electron transport chain.  (^) This mutation further results in the substitution of a histidine for an arginine.  (^) This mutation accounts for approximately half of all cases of LHON.  (^) Three other mutations of mtDNA have also been identified as primary causes of this disease.  (^) Two of these mutations affect other subunits of complex 1, while the third affects cytochrome b which is a component of complex 3.  (^) The mutations causing LHON reduce the capacity of mitochondria to carry out oxidative phosphorylation and generate ATP. LEBER HEREDITARY OPTIC NEUROPATHY:

SYMPTOMS:

 (^) Blindness because of degeneration of optic nerve  (^) Initial thickening of retinal nerve fibre layers and RGC loss within the optic nerve  (^) LHON Plus

DIAGNOSIS AND TREATMENT:

 (^) Neuro-ophthalmological evaluation  (^) Blood testing for mtDNA assessment  (^) A visual eye test  (^) Fundus photography  (^) Optical Coherence Tomography  (^) LHON currently has no proven treatment. Symptomatic treatment and genetic counselling are important in the management of patients with LHON.

SIGNS AND SYMPTOMS:

 (^) CPEO is a rare disease that may affect all ages.  (^) CPEO is the most common symptom of mitochondrial myopathy.  (^) The first presenting symptom of CPEO is Ptosis.  (^) Often, patients will tilt the head backwards to adjust for the slowly progressing ptosis of the lids. In addition, as the ptosis becomes complete, the patients will use the forehead muscle to help elevate the lids.  (^) Weakness of extra ocular muscle including, the orbicularis oculi muscle as well as facial muscles.  (^) Patients may suffer from exposure keratopathy (damage to cornea) the inability to close the eyes tightly.

DIAGNOSIS:

 (^) CPEO is diagnosed by muscle biopsy. On examination of muscle fibers stained with Gömöri trichrome stain, one can see an accumulation of enlarged mitochondria. This produces a dark red staining of the muscle fibers given the name “ragged red fibers”. While ragged red fibers are seen in normal aging, amounts in excess of normal aging give a diagnosis of a mitochondrial myopathy.  (^) Polymerase Chain Reaction also from a sample of blood or muscle tissue can determine a mutation of the mtDNA.

TREATMENT:

 (^) There is currently no defined treatment to ameliorate the muscle weakness of CPEO.  (^) Ptosis associated with CPEO may be corrected with surgery to raise the lids, however due to weakness of the orbicularis oculi muscles, care must be taken not to raise the lids in excess causing an inability to close the lids.

Sign and Symptoms:

 (^) The most common first sign of retinoblastoma is a visible whiteness in the pupil called “cat's eye reflex.”  (^) It also causes strabismus i.e. crossed eyes or eyes that do not point in the same direction, which can cause change in the color of the colored part of the eye (iris).  (^) Other symptoms include redness, soreness, or swelling of the eyelids; and blindness or poor vision in the affected eye or eyes.

TREATMENT:

 (^) Retinoblastoma is often curable when it is diagnosed early. However, if it is not treated promptly, this cancer can spread beyond the eye to other parts of the body. This advanced form of retinoblastoma can be life- threatening.  (^) A novel isoquinoline derivative, EDL-155, was recently evaluated as a potential agent to selectively destroy retinoblastoma cells.  (^) In vitro treatment resulted in mitochondrial disruption and induction of autophagy.  (^) Additionally, the authors demonstrated in vivo treatment efficacy using a rat retinoblastoma model in which EDL-155 suggested localized tumor cell destruction after four periocular injections.

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