Related Experiment Videos
Naphthoquinone cataract in mice: mitochondrial change and protection by superoxide dismutase
Larissa P Martynkina1, Wei Qian, Hitoshi Shichi
1Department of Ophthalmology, Wayne State University School of Medicine, Detroit, Michigan 48201, USA.
Abstract:
An injection of 1,2-naphthoquinone (NQ) into the anterior chamber of mouse eye produces anterior cortical cataract. It was previously shown by histology that mitochondria in lens epithelial cells are the target of ocular drug toxicity. In this work we investigated NQ-induced cataract by closely examining morphological changes of mitochondria and other cellular organelles in the lens epithelium. Mitochondria exhibited marked swelling in 2 hrs after NQ injection but restored the normal condensed configuration at 4.5 hrs. The nuclear chromatin showed condensation at 2 hrs and returned to the normal appearance at 4.5 hrs. This was unexpected because the lens at 4.5 hrs was cataractous due to vacuole formation in fiber cell layers. The result indicates that, although lens epithelial mitochondria are the target of NQ toxicity, cataract begins to develop before mitochondria and other subcellular organelles become totally dysfunctional. At 1 week after NQ injection, most mitochondria disintegrated and the fragmented chromatin appeared to leak out through the ruptured nuclear membrane. SOD injected with NQ significantly delayed the onset of cataract and protected lens epithelial cells. A second SOD injection further delayed cataract development.
Insights
1,2-naphthoquinone (NQ) causes cataracts by damaging lens epithelial cell mitochondria. Cataract development precedes full organelle dysfunction, but superoxide dismutase (SOD) can delay NQ-induced eye damage.
Area of Science:
- Ophthalmology
- Toxicology
- Cell Biology
Background:
- Mitochondria in lens epithelial cells are known targets of ocular drug toxicity.
- 1,2-naphthoquinone (NQ) injection into mouse eyes induces anterior cortical cataracts.
Purpose of the Study:
- To investigate the morphological changes in mitochondria and other cellular organelles following NQ-induced cataract formation.
- To determine the temporal relationship between organelle dysfunction and cataract development.
- To evaluate the protective effects of superoxide dismutase (SOD) against NQ toxicity.
Main Methods:
- Intraocular injection of 1,2-naphthoquinone (NQ) in mouse eyes.
- Morphological examination of lens epithelial cells, mitochondria, and nuclear chromatin at various time points post-injection (2 hours, 4.5 hours, 1 week).
- Administration of superoxide dismutase (SOD) concurrently with or after NQ injection.
Main Results:
- Mitochondria and nuclear chromatin showed transient swelling and condensation, respectively, at 2 hours, returning to normal by 4.5 hours, despite cataract formation due to vacuole development.
- Significant mitochondrial disintegration and nuclear membrane rupture were observed at 1 week post-NQ injection.
- SOD administration significantly delayed cataract onset and protected lens epithelial cells, with a second SOD dose providing further delay.
Conclusions:
- NQ-induced cataract development begins before complete mitochondrial and subcellular organelle dysfunction.
- Lens epithelial cell mitochondria are primary targets of NQ toxicity.
- Superoxide dismutase (SOD) demonstrates a protective effect against NQ-induced ocular toxicity and cataract formation.