Bright Light Damage

Summary: Bright light retinal damage in rodents remains one of the most widely used models mimicking human retinal degenerations such as retinitis pigmentosa (RP) and age-related macular degeneration (AMD).

Model Description

Retinal damage induced by bright light in laboratory rodents has remained one of the most widely used models mimicking human retinal degenerations such as retinitis pigmentosa (RP) and age-related macular degeneration (AMD) for more than five decades.

The model is induced by exposing rodents to bright light (2.500-10.000 lux). The BLE induces the apoptosis of photoreceptors and retinal pigment epithelium1-3. Previous studies have shown that the total retinal thickness decreases with aging, as seen in 7 vs 3.5 month-old mice. Moreover, the BLE exacerbates the retinal damage in aged mice when compared to young mice.

The purpose of this study was to determine whether age, or lifetime exposure to light, is the primary determinant of photoreceptor viability in the BLE model.

Animal speciesMice
Method of inductionExposure to bright light
Follow-up periodUp to 7 days
Route of compound administrationTopical (e.g. eye drops), subretinal, intravitreal, systemic
Read-outs1. In vivo imaging: spectral domain optical coherence tomography (SD-OCT),
2. In vivo functional assessment
3. Morphological assessment,
4. Molecular biology (ELISA, Western blotting, qPCR)

Materials and Methods.

Animals. Young (3.5-month-old) and aged (7-month-old) BALB/c male mice were used in this experiment. Mice were divided into four groups, each group containing 15 mice.

• Group 1: raised in darkness until 3.5-months of age

• Group 2: raised in darkness until 7-months of age

• Group 3: raised in normal lighting conditions (12 h dark – 12 h light) until 3.5-months of age

• Group 4: raised in normal lighting conditions (12 h dark – 12 h light) until 7-months of age

Bright Light Exposure (BLE). Animals were exposed to BLE (10.000 lux) for 12 h.

Electroretinography The functional response of retinal cells was evaluated using flash electroretinography (fERG) (Celeris, Diagnosys LLC, MA, USA) at baseline and 7 days after BLE.

Spectral Domain Optical Coherence Tomography (SD-OCT). The total retinal thickness was measured using SD-OCT (Envisu R2200, Leica-microsystems, IL, USA) at baseline level and 7 days after BLE.

Histology One week after BLE the eyes were enucleated, embedded into paraffin and sectioned. The retinal sections were stained for hematoxylin and eosin (H&E) to verify the morphological differences between the groups

Results

Figure 1. Sample images of the SD-OCT scans taken at baseline and 7 days after BLE.
Fig. 1. Sample images of the SD-OCT scans taken at baseline and 7 days after BLE.
Figure 2. Heat maps depicting the retinal thickness measured from the SD-OCT scans.
Fig. 2. Heat maps depicting the retinal thickness measured from the SD-OCT scans. 7-month-old mice already had a thinner retina at baseline than 3.5-month-old mice. There was a statistically significant decrease in total retinal thickness in young mice exposed to 10 klux light (t-test, P<0.05) as compared to retinal thickness measured before BLE. Aged mice exposed to 10 klux light suffered a dramatic decrease in ONL thickness when compared to the young 10 klux group (t-test, P<0.05). There were no differences in retinal thickness between young mice which were raised in darkness and young control mice after BLE. However aged mice which were kept in darkness were slightly more resistant to intense light exposure than age-matched control mice. Data was analyzed by One-Way ANOVA followed by Tukey’s post-hoc test. S: Superior; T: Temporal; N: Nasal; I: Inferior; X: optic nerve head.
Figure 3. fERG results in young and old mice at baseline and seven days after BLE.
Fig. 3. fERG results in young and old mice at baseline and seven days after BLE. a and b-wave amplitudes decreased after BLE in young and aged groups. Moreover, the level of decrease in the response was similar for the dark and light raised animals. The aged animals grown in darkness maintained the fERG responses as the young ones, while the ones grown in light presented decreased responses.

Conclusions 

Older BALB/c mice are more susceptible to BLE than young BALB/c mice. However, mice raised in absolute darkness had thicker retina and stronger response to flash stimuli than similar age controlled animals. This indicates that both age and light have an impact on retinal viability in BALB/c mice.

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